15 replies to this topic

[Area-1255]

Seems like opiates play a primary role in mediating serotonin induced prolactin release, and being that serotonergic based anti depressants elevate serum and whole beta-endorphin levels...this is the most probable cause, next to oxytocinergic dysfunction in explaining SSRI-induced sexual dysfunction and post-SSRI-induced sexual dysfunction....not sure if this has been discussed before, I just figured I'd throw this out there for all of those suffering from this and perhaps get some opinions on this topic. 

 

EDIT : BETA-ENDORPHIN AND OPIATES also blunt oxytocin release - which is part of why they can be emotionally blunting in high concentrations. http://www.ncbi.nlm..../pubmed/6291011 ~ http://www.ncbi.nlm.nih.gov/pubmed/1971712

 

Seeing as how there a shit ton of people on here complaining of low libido and other issues, and even in cases where one hasn't used SSRI-antidepressants..opiates, particularly endogenous dynorphins and beta-endorphins are a plausible cause of generalized sexual dysfunction...

 

The reason why most remedies may help, but some have such a tough time dealing with these issues..is likely because the central alteration induced by serotonin is hard to reverse , and so one may either be stuck on one remedy but essentially isn't seeing the last part of the bridge, and how to cross it, so to speak.  

 

INSIGHT IS A GOOD THING..AND SPARKS WONDROUS DEBATES.

 

http://www.ncbi.nlm..../pubmed/3621624

 

 

Clin Endocrinol (Oxf). 1986 Nov;25(5):573-8.

Evidence for serotoninergic system involvement in opioid control of luteinizing hormone secretion in man.

Foresta C, Mioni R, Scandellari C.

Abstract

Endogenous opioid peptides tonically inhibit LH by acting on hypothalamic mechanisms which regulate LHRH secretion. Opiates increase hypothalamic serotonin turnover but the involvement of the serotoninergic system in the opioid mechanisms regulating LH secretion in man is not clear at present. This study was designed to evaluate whether the tonic inhibitory effect on LH secretion induced by opiates involves the serotoninergic system. We have studied 10 healthy young men (aged 20-28 years). Five subjects were infused with naloxone (10 mg/h for 3 h) before and 120 min after fenfluramine administration (60 mg orally) on two different occasions. In five other subjects naloxone was infused before and after metergoline pretreatment (8 mg on first and second day and 4 mg on the third day, orally, at 0 time of naloxone infusion). After fenfluramine, naloxone infusion failed to induce any increase in LH plasma levels; metergoline pretreatment significantly enhanced the naloxone-induced LH increase. These data suggest that in man a hypothalamic serotoninergic system may be involved in the opioid mechanisms regulating LH secretion.

PMID:   3621624   [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm..../pubmed/2435887

 

 

J Pharmacol Exp Ther. 1987 Mar;240(3):831-6.

Role of serotonin in opiate-induced prolactin secretion and antinociception in the developing rat.

Bero LA, Kuhn CM.

Abstract

Our laboratory has demonstrated previously that the ability of opiates to stimulate prolactin (PRL) release during ontogeny precedes the appearance of a PRL response to serotonergic drugs. The present study tests the hypothesis that opiates stimulate PRL secretion through a serotonergic mechanism in adult rats, but a nonserotonergic mechanism in neonatal rats. Morphine stimulated PRL secretion in adult and neonatal (10-day-old) rats and this increase was blocked with the opiate antagonist naloxone. Ten-day-old or adult rats were pretreated with the serotonin antagonist, cyproheptadine (CYPRO), or the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Both CYPRO and 5,7-DHT attenuated the PRL response to morphine in adult but not neonatal rats. 5,7-DHT decreased serotonin and 5-hydroxyindoleacetic acid substantially in the hypothalamus. When rats were pretreated with 5,7-DHT several weeks before morphine challenge, serotonin depletion was more pronounced, but the PRL response to morphine was not decreased. In addition, the PRL response to 5-hydroxytryptophan was greatly potentiated, suggesting that functional supersensitivity developed in the 5,7-DHT-treated animals. The ability of CYPRO and 5,7-DHT to block the serotonergic component of a different morphine-induced behavior in the neonate was tested using the tail immersion test for analgesia. Morphine produced profound antinociception in the rat pup which was attenuated markedly by 5,7-DHT and CYPRO. These studies demonstrate that opiates mediate their stimulatory effects on PRL release, at least in part, through a serotonergic mechanism in adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID:   2435887   [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm..../pubmed/8294223

 

 

 

J Androl. 1993 Nov-Dec;14(6):407-10.

Treatment of idiopathic erectile dysfunction in men with the opiate antagonist naltrexone--a double-blind study.

Brennemann W1, Stitz B, Van Ahlen H, Brensing KA, Klingmüller D.

Author information

 

Abstract

Opiate antagonists can indirectly stimulate the secretion of luteinizing hormone (LH) and testosterone, as well as sexual functions in animals and humans. We therefore treated 20 otherwise healthy men with idiopathic erectile dysfunction aged 46.3 +/- 2.7 years (mean +/- SE, range 23.9-63.3) in a double-blind study with an opiate antagonist, naltrexone, or placebo. The erectile dysfunction of these men had persisted for 3.6 +/- 0.5 years despite libido maintenance; standard procedures had excluded any organic causes. Trial duration was 12 weeks overall. After a 4-week forerun, the patients received at first 25 mg naltrexone/day orally or placebo for 4 weeks followed by 4 weeks of a 50-mg dose of naltrexone/day or placebo. Each day the patients filled out a questionnaire detailing libido, degree of erection, frequency of sexual intercourse, and spontaneous morning erections. Serum concentrations of gonadotropins and testosterone were determined radioimmunologically in the initial stage and at the end of each phase. Both patient collectives had similar initial factors. The group treated with naltrexone showed a significant rise in spontaneous early morning erections during the treatment: from 2.8 +/- 0.3 to 4.2 +/- 0.3 a week (P < 0.001). The placebo group showed no significant change in spontaneous erections (2.4 +/- 0.3 and 2.6 +/- 0.3, respectively). The subjective parameters, however, such as libido, degree of erection, and frequency of sexual intercourse showed no significant difference within each group. There was no difference in LH, follicle-stimulating hormone, or testosterone concentrations in both groups. Thus, treatment with naltrexone significantly raises the rate of spontaneous early morning erections when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID:   8294223   [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/10371024

 

 

Farmaco. 1999 Mar 31;54(3):130-3.

Serum beta-endorphin level in patients with depression on fluvoxamine.

Djurović D1, Milić-Askrabić J, Majkić-Singh N.

Author information

 

Abstract

The main interest of the present study was to determine possible alternations in beta-endorphin serum levels in healthy volunteers and in patients with depression, as well as changes in beta-endorphin serum levels caused by fluvoxamine treatment. Fluvoxamine maleate (Fevarin) was administered orally at a dose of 200 mg/day for 4 weeks. The serum levels of beta-endorphin were lower in patients with 'nonendogenous' depression (104.68 +/- 5.29 pg/ml) and those with 'endogenous' depression (36.34 +/- 2.23 pg/ml) than in healthy volunteers (125.19 +/- 1.64 pg/ml). The endogenously depressed patients had significantly lower beta-endorphin levels than the nonendogenous patients. A 4-week treatment of fluvoxamine (200 mg/day) caused a statistically significant increase in beta-endorphin serum levels in all patients (nonendogenous depression 132.10 +/- 2.38 pg/ml and endogenous depression 50.09 +/- 2.45 pg/ml) in comparison to values found before the onset of the therapy. The efficacy of fluvoxamine was 11.0 (+/- 9.0) evaluated by the Hamilton Rating Scale for Depression (HAMD) in the patients with a diagnosis of depression. These results indicate that determination of beta-endorphin serum levels could be a valuable laboratory test in the diagnosis of depression.

PMID:   10371024   [PubMed - indexed for MEDLINE]

 

Edited by Area-1255, 30 October 2014 - 04:15 AM.

[forexworld12]

Hi Jason, There's some new theory on the other forum as to why we need an agonist or partial agonist instead of antagonist like way 100635 - what do you think about it? 

 

What is the main thing causing this problem - PSSD?

It is inhibition of dopamine receptors in general, particularly in and around the Raphe nucleus. They are not damaged, they are not desensitized, there is nothing wrong with dopamine binding, and it is more complicated than there just not being enough dopamine release into the synapse.

It is actually being inhibited. So it doesn't just release too little as a continual problem, when levels increase, they increase by lower a percentage. This is the basis for much of what people experience in different ways, due to differing genes. The main idea is the dopamine release is being inhibited. So those other dopamine receptors down the line aren't getting what they need.

Serotonin receptors inhibit dopamine. That is because they act as a method of regulation. The more serotonin that binds to the heteroreceptor, the more dopamine release is inhibited. This receptor accepts binding of different neurotransmitters in different places, which have different affects on it, including regulation of dopamine release.

So why is an excessive amount of serotonin in the synapse, binding to the heteroreceptor?

It is because the autoreceptor is releasing too much serotonin into the synapse. So we have to figure out why that is. The autoreceptor is regulated by the same neurotransmitter, in this case serotonin. So the amount of serotonin which binds to it, controls how much serotonin it releases. Serotonin is generally inhibitory. So the more activation of this receptor, the more it's release of serotonin is inhibited.

The main cause of PSSD is the receiving part of the autoreceptor being desensitized. So the normal amount of serotonin that was the right amount to do the job, now causes LESS activation of the receptor, and therefore it's inhibitory effect on serotonin release is INSUFFICIENT.

Our autoreceptors didn't go back to normal. They are stuck in that  desensitized state. So the normal amount of serotonin which has always been there is not enough to do the job.

So in order to get the same amount of activation you had before, you must have MORE serotonin there than is normal.  You have to compensate for that lack of sensitivity. 

It's kind of like when a button on a remote wears out. The normal amount of pressure won't send the signal. You have to press harder to get it to work. In the same way, we have to press harder on the autoreceptor.

Agonism is not the same as reuptake inhibition. The former just means there is more there, but it is taken up normally. The latter means it is not taken up normally, and it builds up too quickly, too much.

So an antagonist on the autoreceptor is going to exacerbate the very problem you have. You can't press the button more softly. You need an agonist, to inhibit the release of the receptor the same amount it used to before you got PSSD.

[Area-1255]

Hi Jason, There's some new theory on the other forum as to why we need an agonist or partial agonist instead of antagonist like way 100635 - what do you think about it? 

 

What is the main thing causing this problem - PSSD?

It is inhibition of dopamine receptors in general, particularly in and around the Raphe nucleus. They are not damaged, they are not desensitized, there is nothing wrong with dopamine binding, and it is more complicated than there just not being enough dopamine release into the synapse.

It is actually being inhibited. So it doesn't just release too little as a continual problem, when levels increase, they increase by lower a percentage. This is the basis for much of what people experience in different ways, due to differing genes. The main idea is the dopamine release is being inhibited. So those other dopamine receptors down the line aren't getting what they need.

Serotonin receptors inhibit dopamine. That is because they act as a method of regulation. The more serotonin that binds to the heteroreceptor, the more dopamine release is inhibited. This receptor accepts binding of different neurotransmitters in different places, which have different affects on it, including regulation of dopamine release.

So why is an excessive amount of serotonin in the synapse, binding to the heteroreceptor?

It is because the autoreceptor is releasing too much serotonin into the synapse. So we have to figure out why that is. The autoreceptor is regulated by the same neurotransmitter, in this case serotonin. So the amount of serotonin which binds to it, controls how much serotonin it releases. Serotonin is generally inhibitory. So the more activation of this receptor, the more it's release of serotonin is inhibited.

The main cause of PSSD is the receiving part of the autoreceptor being desensitized. So the normal amount of serotonin that was the right amount to do the job, now causes LESS activation of the receptor, and therefore it's inhibitory effect on serotonin release is INSUFFICIENT.

Our autoreceptors didn't go back to normal. They are stuck in that  desensitized state. So the normal amount of serotonin which has always been there is not enough to do the job.

So in order to get the same amount of activation you had before, you must have MORE serotonin there than is normal.  You have to compensate for that lack of sensitivity. 

It's kind of like when a button on a remote wears out. The normal amount of pressure won't send the signal. You have to press harder to get it to work. In the same way, we have to press harder on the autoreceptor.

Agonism is not the same as reuptake inhibition. The former just means there is more there, but it is taken up normally. The latter means it is not taken up normally, and it builds up too quickly, too much.

So an antagonist on the autoreceptor is going to exacerbate the very problem you have. You can't press the button more softly. You need an agonist, to inhibit the release of the receptor the same amount it used to before you got PSSD.

He's somewhat correct in terms of HOW MUCH SEROTONIN is being released and in contrast to dopamine, this is one method that can be used is the agonism of 5-HT1A's - but...the problem is that 5-HT1A receptors, regardless of how sensitized or de-sensitized they are, always have an anti sexual effect, which often times is enough to OVER RIDE and OVER POWER the serotonin reduction caused by agonism.

 

 

 

http://www.ncbi.nlm..../pubmed/1357709

Psychopharmacology (Berl). 1992;108(1-2):47-50.

5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.

Simon P1, Guardiola B, Bizot-Espiard J, Schiavi P, Costentin J.

Author information

 

Abstract

The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.

PMID:   1357709   [PubMed - indexed for MEDLINE]

Thus, dopamine agonists do you no good, nor does dopamine, when 5-HT1A is being stimulated/agonized...

 

PARADOXICALLY, 1A agonists may benefit libido and sexual behavior by temporarily altering the balance between dopamine and serotonin, however....it's tricky, because....if one is to agonize the 5-HT1A, then there is always the chance it will come back to bite you eventually, by directly inhibiting erectile response induced by dopamine....

 

 

The difference between agonism and antagonism, they both have their benefits....but agonism is altering the LEVEL of serotonin, in terms of reduction, in the process, agonism of 1A also attaches to dopamine and GABAergic terminals, reducing both of these as well!

 

 

An antagonist would raise serotonin, HOWEVER, it would also greatly reduce cortisol, prolactin, and it would stop excessive endorphin production that would reduce sex hormones......

 

WAY 100 635, being also a dopamine agonist - would help to restore both potency and libido, by blocking 1A - the separate effect is enough to over ride the pro serotonin effect.

 

BOTTOM LINE IS - EVEN IF WE ACHIEVE BENEFIT BY REDUCING SEROTONIN BY 1A AGONIST ---- WHAT GOOD IS IT IF WE ARE PREVENTING THE BENEFITS OF DOPAMINE ON ANOTHER LEVEL?

 

http://www.jneurosci...3/5488.full.pdf

 

 

 

http://www.jneurosci...3/5488.full.pdf

http://www.ncbi.nlm....les/PMC1909390/

 

Serotonin 5-HT1A Receptors Regulate NMDA Receptor

Channels through a Microtubule-Dependent Mechanism

Eunice Y. Yuen, Qian Jiang, Paul Chen, Zhenglin Gu, Jian Feng, and Zhen Yan

Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14214

The serotonin system and NMDA receptors (NMDARs) in prefrontal cortex (PFC) are both critically involved in the regulation of

cognition and emotionunder normal and pathological conditions; however,theinteractions betweenthem are essentiallyunknown.Here

we show that serotonin, by activating 5-HT1A receptors, inhibited NMDA receptor-mediated ionic and synaptic currents in PFC pyramidal

neurons, and the NR2B subunit-containing NMDA receptor is the primary target of 5-HT1A receptors. This effect of 5-HT1A receptors

was blocked by agents that interfere with microtubule assembly, as well as by cellular knock-down of the kinesin motor protein KIF17

(kinesin superfamily member 17), which transports NR2B-containing vesicles along microtubule in neuronal dendrites. Inhibition of

either CaMKII (calcium/calmodulin-dependent kinase II) or MEK/ERK (mitogen-activated protein kinase kinase/extracellular signalregulated

kinase) abolished the 5-HT1A modulation of NMDAR currents. Biochemical evidence also indicates that 5-HT1A activation

reduced microtubule stability, which was abolished by CaMKII or MEK inhibitors. Moreover, immunocytochemical studies show that

5-HT1A activation decreased the number of surface NR2B subunits on dendrites, which was prevented by the microtubule stabilizer.

Together, these results suggest that serotonin suppresses NMDAR function through a mechanism dependent on microtubule/kinesinbased

dendritictransport of NMDA receptorsthat is regulated by CaMKII and ERK signaling pathways. The 5-HT1A–NMDAR interaction

provides a potential mechanism underlying the role of serotonin in controlling emotional and cognitive processes subserved by PFC.

Key words: trafficking; KIF17; MAP2; Ca 2/calmodulin-dependent kinase II; MAP kinase; prefrontal cortex; siRNA; a

 

Pharmacol Biochem Behav. 1994 May;48(1):203-7.

Penile erection and yawning induced by paraventricular NMDA injection in male rats are mediated by oxytocin.

Melis MR1, Stancampiano R, Argiolas A.

Author information

 

Abstract

The effect of N-methyl-D-aspartic acid (NMDA), (+-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), or (+-)-trans-1-amino-1,3-cyclo-pentanedicarboxylic acid (ACPD) (5-60 ng in 0.3 microliter of saline) microinjected in the paraventricular nucleus of the hypothalamus on penile erection and yawning was studied in male rats. NMDA induced both penile erection and yawning in a dose-dependent manner. AMPA and ACPD also induced penile erection but less potently than NMDA, but were ineffective in causing yawning. NMDA effect on penile erection and yawning was prevented by (+)-MK-801 (0.05-0.1 mg/kg IP, 10 min before NMDA), by the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8- vasotocin (50-100 ng ICV 10 min before NMDA), but not by haloperidol (0.1-0.5 mg/kg IP 10 min before NMDA). The results suggest that NMDA induces penile erection and yawning by increasing oxytocinergic transmission by acting in the paraventricular nucleus of the hypothalamus.

PMID:   7518086   [PubMed - indexed for MEDLINE]

 

Edited by Area-1255, 11 December 2014 - 09:51 PM.

[Area-1255]

THE ISSUE IS 5-HT1A AGONISTS REDUCE BOTH NMDA AND DOPAMINE..WHICH ARE NECESSARY FOR SEXUAL FUNCTION.

Why do you think many people don't respond to BUSPAR or 1A agonists....?

[Area-1255]

http://onlinelibrary...bjp.0703510/pdf

 

Serotonin inhibition of the NMDA receptor/nitric oxide/cyclic

GMP pathway in human neocortex slices: involvement of 5-HT2C

and 5-HT1A receptors

*,1Guido Maura, 1

Manuela Marcoli, 1

Olimpia Pepicelli, 1

Christian Rosu, 2

Concetta Viola & 1

Maurizio Raiteri

1

Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, UniversitaÁ di Genova, Viale Cembrano 4, 16148

Genova, Italy and 2

Clinica Neurochirurgica, UniversitaÁ di Genova, Ospedale S. Martino, Largo Rosanna Benzi 10, 16132 Genova,

Italy

1 The NMDA receptor/nitric oxide (NO)/cyclic GMP pathway and its modulation by 5-

hydroxytryptamine (5-HT) was studied in slices of neocortical samples obtained from patients

undergoing neurosurgery.

2 The cyclic GMP elevation produced by 100 mM NMDA was blocked by 100 mM of the NO

synthase inhibitor NG-nitro-L-arginine (L-NOARG) or by 10 mM of the soluble guanylate cyclase

inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a] quinoxaline-1-one (ODQ).

3 The NMDA eect was prevented by 5-HT or by the 5-HT2 agonist (+)-1-(2,5-dimethoxy-4-

iodophenyl)-2-aminopropane ((+)-DOI; EC50=22 nM). The (+)-DOI inhibition was insensitive to

the 5-HT2A receptor antagonist MDL 100907 or the 5-HT2B antagonist rauwolscine; it was largely

prevented by 1 mM of the non-selective 5-HT2C antagonists mesulergine (5-HT2A,B,C), ketanserin (5-

HT2A,C) or SB 200646A (5-HT2B,C); it was completely abolished by 0.1 mM of the selective 5-HT2C

receptor antagonist SB 242084.

4 The NMDA-induced cyclic GMP elevation also was potently inhibited by the selective 5-HT2C

agonist RO 60-0175 and by the antidepressant trazodone, both added at 1 mM, in an SB 242084-

sensitive manner.

5 Finally, the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 1 mM)

inhibited the NMDA-evoked cyclic GMP response, an effect blocked by the selective 5-HT1A

receptor antagonist WAY 100635.

6 In conclusion, the NMDA receptor/NO/cyclic GMP pathway in human neocortex slices can be

potently inhibited by activation of 5-HT2C or 5-HT1A receptors.

British Journal of Pharmacology (2000) 130, 1853 ± 1858

Keywords: human neocortex; 5-hydroxytryptamine-gluta

 

 

[Area-1255]

http://www.jbc.org/c...7/39/36553.full

 

 

 In this study, we revealed the 5-HT_1A-mediated reduction of AMPA receptor currents, which provides a potential mechanism for the inhibitory role of 5-HT_1A receptors on PFC pyramidal neuron activity (1). Our previous studies show that 5-HT₂ and 5-HT₄ receptors are linked to the regulation of γ-aminobutyric acid, type A receptor function in PFC via a PKC- and PKA-mediated mechanism, respectively (18, 49). The specific coupling of these receptors to various signaling pathways provides serotonin with a precise and flexible mechanism to regulate different ion channels. By doing so, serotonin can simultaneously remodel excitability in a functionally appropriate manner.

Multiple signaling pathways have been found with the activation of 5-HT₁receptors, including the inhibition of adenylyl cyclase and stimulation of the mitogen-activated protein kinase (50). Our results with PKA activators and inhibitors suggest that the 5-HT_1A-mediated reduction of AMPA receptor currents is dependent on PKA inhibition. Previous studies have shown that PKA phosphorylation of GluR1 subunit at Ser⁸⁴⁵ enhances AMPA currents (35), giving the possibility that the 5-HT_1Areduction of AMPA currents is directly due to the decreased GluR1 phosphorylation by PKA. However, the blockade of 5-HT_1Aeffects on AMPA currents by PP1 inhibitors suggests that this modulation requires the activation of PP1.

 

[forexworld12]

Brother These 2 studies - 

 

http://www.ncbi.nlm....pubmed/24180393

 

http://www.ncbi.nlm....pubmed/19829169

 

what do you think -   HTR1A is simply the piece of genetic code that codes the 5HT-1A receptor.  The receptors are always being replaced and new ones are being made. They are being MADE desensitized, they aren't the same ones we had while on the med .. IF there is any way Change the HTRIA gene that would be the ultimate cure !

 

Can you comment on this study too - http://www.ncbi.nlm....pubmed/17873550   ..  can exercise work ?

[Area-1255]

Brother These 2 studies - 

 

http://www.ncbi.nlm....pubmed/24180393

 

http://www.ncbi.nlm....pubmed/19829169

 

what do you think -   HTR1A is simply the piece of genetic code that codes the 5HT-1A receptor.  The receptors are always being replaced and new ones are being made. They are being MADE desensitized, they aren't the same ones we had while on the med .. IF there is any way Change the HTRIA gene that would be the ultimate cure !

 

Can you comment on this study too - http://www.ncbi.nlm....pubmed/17873550   ..  can exercise work ?

All neurotransmitter receptors are linked to "pieces of genetic code", brother, you need to research genetics/geneology and such, they are really interesting fields!

Our genes are determined by long-histories within our families specific culture, hormone distribution, eating habits etc...

For example, if one person on your mothers side, way down the line, at tons of carbohydrates (breads , donuts etc namely) - then this is going to contribute to genes passed down to the child in terms of insulin receptors....then if everyone after her ate a similar diet, we are looking at 10x the gene changes, or twice added on for each! 

 

The significance wouldn't be as rivaled in terms of neurotransmitters, but for example, some icelandic folks, and interestingly, some alaskan citizens, have been known to be born without aromatase , the enzyme that converts testosterone to estrogen --- thus, many of them grow to be very very tall, because estrogen normally fuses the epiphyiseal growth plates !

 

Some men , who may also have autistic type syndrome, may be born with a cytochrome P450 mutation and others(CX5/xc17), that results in something called "Prader-Willi"  230px-Prader_Willi_Facial_Features.png   64.1KB   1 downloads  (http://en.wikipedia....–Willi_syndrome)

 

 

The odd facial features in this condition once prompted people to believe that prader-willi was a manifestation of the "Nephilium" - or , humans born with half angel or half demon in them. 

 

 

The point is brother, all of our neurotransmitter receptors are merely gene sequences, and though as humans, we all have similarities, we also have many differences.....we should be focusing on our individuality, and what works for us to take every possible advantage of our genes, we all should be working to be fit, and healthy - so that we can maximize our potential!

 

 

 

"This , is an important time to be alive., a time where the brave amongst the youth rise to a greater understanding of how our conscience is truly mapped, a time where beliefs are fought for, a time where people separate and divide and yet come together, a time where we find our place along with the secrets of the lost worlds."

 

 

 

 

Transhumanist, immortalist, fitness enthusiast, strength athlete and researcher alike, or just someone looking to solve a nagging health issue - we all have some progress to be made - and we need to make sure we are doing everything in our power to coordinate and realize that progress!

Edited by Area-1255, 13 December 2014 - 07:20 PM.

[forexworld12]

A very nice post brother !

 

so basically Genes have nothing to do with PSSD ?

 

but can change our genes to optimal level or improve it ? like the HTRIA that is the serotonin auto-receptor gene ... if it makes more gene is it making it de-sentisized ? 

[Area-1255]

A very nice post brother !

 

so basically Genes have nothing to do with PSSD ?

 

but can change our genes to optimal level or improve it ? like the HTRIA that is the serotonin auto-receptor gene ... if it makes more gene is it making it de-sentisized ? 

On the contrary, genes do have a ton to do with it...

Some people have just very poor metabolism of serotonin, some people are born with COMT mutations that make for a more anxiogenic (anixety prone) environment, some people have variants of the MAO-A gene, one is called the WORRIER gene, and one is the WARRIOR gene, the worrier gene creates more monoamine oxidase, or in some rarer cases, a deletion of one allele leading to disruption or instabilization of the MAO-A, leading to more less breakdown of serotonin, norepinephrine - leading to literally, more worrying!

 

The warrior gene is missing an allele , or it could also involve a shorter strand of the gene encoding the MAOA, also leading to effects typical of an average person taking an MAO inhibitor drug for long periods of time. 

 

Additionally, having prader-willi, klinefelters, androgen insensitivity syndrome and many more may increase the susceptibility to PSSD, though some variants of prader willi have almost no serotonin being produced, as their livers rapidly deactivate tryptophan hydroxylase and they often have a vitamin D DEFICIENCY that never is treated due to behavioral problems.

 

% I dunno.

 

Point blank, instead of attempting sleep deprivation, or vain, stressful countermeasures in attempt to "re-code" the 5HT1A receptor, why not just do the things that will restore its function in the first place?

 

When you restore testosterone to normal or high - normal, and cortisol and estrogen drop down, then your 5-HT1A receptors will normalize.

 

 

 

Eur J Neurosci. 1998 Aug;10(8):2685-93.

5HT1A-receptors and behaviour under chronic stress: selective counteraction by testosterone.

Flügge G1, Kramer M, Rensing S, Fuchs E.

Author information

 

Abstract

Behaviour of chronically stressed male tree shrews is characterized by a reduction in scent marking, self-grooming and overall locomotor activity. It has been proposed that this subordination behaviour is related to the down-regulation of 5HT1A-receptors occurring in distinct brain regions of the animals. The high cortisol concentrations which accompany chronic stress are supposed to induce 5HT1A-receptor down-regulation. Because chronic stress in males also decreases androgen levels we investigated whether behaviour and 5HT1A-receptor expression could be renormalized by testosterone replacement. Male tree shrews were submitted to subordination stress for 28 days, while during the last 18 days, one group was treated with testosterone and one with vehicle. Scent marking, self-grooming, and overall locomotor activity were monitored, and cortisol levels were measured in morning urine during the whole experiment. Brain 5HT1A-receptors were quantified by in vitro receptor autoradiography. Although in subordinate animals cortisol levels remained high during the testosterone treatment, 5HT1A-receptors in the hippocampal formation and the occipital cortex were renormalized to control levels by the androgen, but 5HT1A-receptors in the ventromedial thalamic nucleus did not return to base line levels. Scent marking and self-grooming behaviour were both renormalized by testosterone, but overall locomotor activity did not return to base line levels. These data indicate that a balance between glucocorticoids and androgens is necessary to maintain 'normal' numbers of the monoamine receptors. The fact that both, 5HT1A-receptors and certain behaviours can be renormalized by the sex steroid supports the view that 5HT1A-receptor are involved in the regulation of stress behaviour. However, the fact that overall locomotor activity was not returned to baseline indicates that different types of behaviour are distinctly regulated.

PMID:   9767398   [PubMed - indexed for MEDLINE]

This means that if your receptors are messed up , testosterone will normalize them.

 

Once you get estrogen down to  an acceptable range, then things will start falling into balance...

 

ALOT of the "wrong" serotonin receptors are increased by excess estradiol - helping to contribute to the problems high estrogen gives..

Edited by Area-1255, 13 December 2014 - 07:42 PM.

[forexworld12]

Thanks brother .. 

 

BTW I was prescribed nothing for increasing testosterone? .... It's 5 pg/ml( very low)   I want it like 20-25 pg/ml ... This target is still not high ..it's still Within the normal range according to my clinic's report range !

 

Other thing I don't know is the hormones meds - is it the same stuff like as long as one is taking it every hormone will be optimal but once if i quit the meds will the imbalance happen again ?

 

 

 You mean there's no point to try to re-code 5HTIA receptor - If I fix hormone everything else will normalize sure shot ?   

 

 

[Area-1255]

 

Thanks brother .. 

 

BTW I was prescribed nothing for increasing testosterone? .... It's 5 pg/ml( very low)   I want it like 20-25 pg/ml ... This target is still not high ..it's still Within the normal range according to my clinic's report range !

 

Other thing I don't know is the hormones meds - is it the same stuff like as long as one is taking it every hormone will be optimal but once if i quit the meds will the imbalance happen again ?

 

 

 You mean there's no point to try to re-code 5HTIA receptor - If I fix hormone everything else will normalize sure shot ?   

 

Once you start the aromatase inhibitor , estrogen falls and testosterone rises, my recommendation is, a few days or a week in , you start working out hard again - once you get your test at a higher level - and you start lowering body fat, you will surely reduce the problem in a permanent manner - raising your testosterone will give you the edge, but to keep it in good order, take advantage of that testosterone , reduce body fat, lift weights,,, all of this will ensure more permanent results...you don't have to take an anti-estrogen permanently, but once you get your body fat down and boost your confidence, muscle etc..you will really get more permanent results!

 

By reducing body fat , your estrogen receptors decrease, and by building muscle, your receptors for testosterone increase!

[forexworld12]

 

 

Thanks brother .. 

 

BTW I was prescribed nothing for increasing testosterone? .... It's 5 pg/ml( very low)   I want it like 20-25 pg/ml ... This target is still not high ..it's still Within the normal range according to my clinic's report range !

 

Other thing I don't know is the hormones meds - is it the same stuff like as long as one is taking it every hormone will be optimal but once if i quit the meds will the imbalance happen again ?

 

 

 You mean there's no point to try to re-code 5HTIA receptor - If I fix hormone everything else will normalize sure shot ?   

 

Once you start the aromatase inhibitor , estrogen falls and testosterone rises, my recommendation is, a few days or a week in , you start working out hard again - once you get your test at a higher level - and you start lowering body fat, you will surely reduce the problem in a permanent manner - raising your testosterone will give you the edge, but to keep it in good order, take advantage of that testosterone , reduce body fat, lift weights,,, all of this will ensure more permanent results...you don't have to take an anti-estrogen permanently, but once you get your body fat down and boost your confidence, muscle etc..you will really get more permanent results!

 

By reducing body fat , your estrogen receptors decrease, and by building muscle, your receptors for testosterone increase!

 

Thanks man .. 

 

Hmm Do you know how much free testo can rise by the aromatase inhibitor ? I'm guessing not x400 .. I was thinking about clomid as an add on you know ! Also I was prescribed nothing for increasing Sex hormone-binding globulin - it's half of the lowest level .. or is it like that will fall into place too .. It's great to know testo treatment can normalize 5ht1a expression in some areas of the brain ...

 

I was wondering if high estrogen/prolactin  can make the 5HTIa autoreceptor dysfunctional ?

[Area-1255]

 

 

 

Thanks brother .. 

 

BTW I was prescribed nothing for increasing testosterone? .... It's 5 pg/ml( very low)   I want it like 20-25 pg/ml ... This target is still not high ..it's still Within the normal range according to my clinic's report range !

 

Other thing I don't know is the hormones meds - is it the same stuff like as long as one is taking it every hormone will be optimal but once if i quit the meds will the imbalance happen again ?

 

 

 You mean there's no point to try to re-code 5HTIA receptor - If I fix hormone everything else will normalize sure shot ?   

 

Once you start the aromatase inhibitor , estrogen falls and testosterone rises, my recommendation is, a few days or a week in , you start working out hard again - once you get your test at a higher level - and you start lowering body fat, you will surely reduce the problem in a permanent manner - raising your testosterone will give you the edge, but to keep it in good order, take advantage of that testosterone , reduce body fat, lift weights,,, all of this will ensure more permanent results...you don't have to take an anti-estrogen permanently, but once you get your body fat down and boost your confidence, muscle etc..you will really get more permanent results!

 

By reducing body fat , your estrogen receptors decrease, and by building muscle, your receptors for testosterone increase!

 

Thanks man .. 

 

Hmm Do you know how much free testo can rise by the aromatase inhibitor ? I'm guessing not x400 .. I was thinking about clomid as an add on you know ! Also I was prescribed nothing for increasing Sex hormone-binding globulin - it's half of the lowest level .. or is it like that will fall into place too .. It's great to know testo treatment can normalize 5ht1a expression in some areas of the brain ...

 

I was wondering if high estrogen/prolactin  can make the 5HTIa autoreceptor dysfunctional ?

 

Aromatase inhibitors would lower sex-hormone-binding-globulin - which would increase free testosterone ------- !

 

You DO NOT WANT TO RISE SHBG, EVEN IF IT IS LOW - IT WILL NORMALIZE AS YOU LOWER ESTROGEN AND PROLACTIN!

 

Yes, high estrogen causes serotonergic / dopaminergic dysfunctions. Including the autoreceptor.

[a355584]

Looking for a cure: are why focusing on the right way?

Everyone knows the main theory about the pathogenesis of PSSD: the excessive release of serotonin (which has a mixed but essentially inhibitory role on sexual functions) by the serotonergic neurons (concentrated in the raphe nuclei of the midbrain) caused the "desensitization" of 5-HT1A autoreceptors (that act as sentinels that regulate the release of a substance according on how much there is already in circulation, this mechanism is also called negative feedback)[1].
The "down regulation" of the 5-HT1A autoreceptors is instead caused by chronic and excessive activation by its natural "agonist" (serotonin) that is made available in abnormal quantities by the use of SSRIs. It is therefore natural to think to the autoreceptors as something that is "damaged" by excessive competition and that can be cured using an antagonist that lead him to be again "sensitive."

At this point that we have to do a reflection: the autoreceptor is a sentinel, a switch that if "on" sends a chemical signal. What the cell (neuron) have to do when it receives this chemical signal is written in the genes, that is in the sequence of the DNA; how much it should do (that is, how much to increase or decrease the release of serotonin) it depends on the genes expression.
Essentially two mechanism regulate gene expression:

• Binding of chemical groups directly to DNA (covalently) that function as silencers or activators. The main inhibitor is the methyl group that, binding at particular points of the promoter sequences, silences gene expression. The protein that bind methyl groups to DNA is the DNMT.

• The other is the tangling of the DNA around proteins (called histones): if the DNA is wrapped on itself, the molecular machines that should read the instruction contained in the DNA, cannot bind the DNA because there isn’t sufficient space. The ability of a histone to compact a DNA molecules (and thus repress gene expression) depends on the presence of particular molecules bound to the histone. The main one is the acetate group: if it binds to histone, forces him to expand and so molecular machines can come in and gene expression is activated.

The acetyl groups are linked to histone by HAT and detached from it by HDAC. Also histones can be methylated in some particular positions, and this has mixed effects on gene expression.

SSRIs activate gene silencing

It’s well known that SSRIs activate the gene-silencing mechanisms. During the assumption has been seen[2][3][4][5][6][7][8][9][10]:

• Increase in the expression of certain proteins that carry methyl groups (called MeCP2 and MBD1)

• Increase the mRNA synthesis of HDAC2 gene (the HDAC of a particular subtype of histone)

• There’s a decreased acetylation in the histone "H3" in three areas of serotonin projection: the caudate-putamen (striatum), the frontal cortex and the dentate gyrus (5-HT neurons are extensively arborized, and their axons reach all brain areas).

All this suggests the induction of gene silencing.
Now we can rethink to the neuron such a stubborn person who does something of wrong: we told him to correct his behavior (the autoreceptor send his message to the cell) but he will not change his behavior (excessive release of serotonin) because he is a person who does not listen what we told to him (reduced gene expression).

So we cannot think to reactivate the negative feedback mechanism only binding them an antagonist because who is stuck in a situation of "off" is not the autoreceptor, but the DNA is to be.

The right strategy therefore have to be the reactivation of gene plasticity which can then be guided in the right direction by the use of an antagonist of the 5-HT1A autoreceptors.

A possible partial theoretical confirmation of this hypothesis is the results of a study in which rats whit an animal model of tardive dyskinesia (a disorder in some ways similar to the PSSD) had a partial remission of the disease using a HDAC inhibitor[11].

How to induce gene expression plasticity

Firstly, we recall the main objectives:

• To promote the demethylation of DNA by inhibiting DNMT: the new synthesized DNA is less methylated and then whit an increased gene expression.

• Inhibit the deacetylation of histones, in particular inhibiting HDAC

• Encourage the acetylation of histones, in particular by increasing the activity of HAT

It has also been seen that the increase of histone acetylation is accompanied by a demethylation of DNA, that is, the two events have a synergistic effect[12]. It 'important to note first of all that these effects are time and dose dependent, ie the effects are proportional to the dose taken and manifests itself after some time.

Several compounds can do this. Most of them are natural occuring compounds and found in green tea but this does not mean that they are little effective: some are very promising for the treatment of other diseases in which the gene expression change is crucial. Other are drugs are already used for other purposes[13][14][15][16][17][18][19][20][21][22].
Unlucky, often they have a low biodisponibility and a short half-life, than high and multiple doses should be necessary.
Most promising are listed for first.

 

EPIGALLOCATECHINE GALLATE (EPCG)

One of most studied, well caracterized and most effective natural compound that influence gene expression. Is one of major component of green tea extract. It can easily cross blood-brain barrier and is demonstrated that directly bind DNA^19[23][24][25]. It is DNMT1, DNMT3, HDAC1 inhibitor and a MeCP2 inhibitor using Mg²⁺ as cofactor. Increase amount of glutathione and indirectly the acetilation of histone H3 and H4. Unlucky it is also a weak inhibitor of HAT, has a very low biodisponibility and may be hepatotoxic. Has been demonstrated that minimum effective dose in order to induce genetic effect is 800 mg 2 times a day. The ingestion of high grade, dried green extract, which contains a lot of different catechine, gallate and flavonoid, is more effective then the ingestion of pure EPGC: all the “gallate” and “chatechin” compounds are generally HDAC and DNMT inhibitor and they have a synergistic effect. They’re generally recognized as safe.

QUERCITINE

A flavonoid, is a strong enhancer of H3 and H4 histone acetylation, thus activates SIRT1 and SIRT6 mediated deacetylation; Inhibit DNMT and LSD1 (histone demethylating protein). It is also a weak MAOI. Was found to be active at a concentration of 75-100 um.

GENISTEINA (and less DAIDZEINE and BIOCIANINE A)

They are phytoestrogens and belongs to the category of isoflavones. They are strong inhibitor of HDAC (mostly HDAC1) and DNMT (mostly DNMT1 and DNMT3); less strong inhibitor of MeCP2. Was proved to demethylate ipermethylated genomes without lead to ipomethylation. It has a strong and synergic effect whit other DNMT and HDAC inhibitor.
It is an estrogen receptor agonist and then may produce non-hormonal effects.

SODIUM BUTIRRATE

It is a strong and natural occurring HDAC inhibitor and one of most studied. It has a lot of other positive effects and has been demonstred to be neuroprotective.

VALPROATE and SULPIRIDE

Valproate is an anticonvulsive and a mood stabilizer drug that act as a strong HDAC inhibitor and this may account of its anticonvulsive and mood stabilizing effects. Sulpiride is a very effective antidepressant (I want to recommend to everyone because is a fantastic drug whit a rapid onset and persisting effect specially on ruminative though, anxiety and bad feeling). It was found that a combination of the two drugs in clinically relevant doses activate brain demethylation. This effect was studied on GABA neurons but may occur also in other type of neurons[26][27][28].

CURCUMINE

Strong inhibitor of HDAC, HAT, DNMT, MeCP2. Has been shown to be able to induce demetilation of hypermethylated zone of DNA, in a stronger way than genisteine. Because its potent HAT inhibitor activity it may be a second line treatment or can be used to prevent ssri’s induced modification of genetic expression.

LUTEOLINE

Luteolin is a flavone, a type of flavonoid. Increase histone acetylation, particularly H3 e H4, inhibiting their HDAC and activating SIRT6-mediated deacetylation; Inhibit DNMT and LSD1 (histone demetylating protein). Thus, weak diminish phosporylation on H3 and H4 and is a weak indirect antagonist of DNMT.

APIGENINE

A flavone, is a HDAT inhibitor (soprattuto H1 and H3) and weak activator of SIRT6 mediated deacetylation. Apigenin may also stimulate adult neurogenesis. Concentration over 5-10 um are not recommended because gaba agonism and other central effects. It is a weak MAOI.

DIALLIL SULFIDE, ANACARDIC ACID and GARLIC

A lot of compounds in garlic and broccoli are HDAC and DNMT inhibitor, then high grade dried garlic extract and to eat broccoli may be strongly recommended.

SAM, vitamins B and ZINC

S-Adenosil-Methionine is the natural transporter of methyl groups and work in a synergic way whit DNMT, than induce methylation. Its natural counterpart is S-Adenosil-Omocisteine, a strong demethylating agent which expression increase during the use of HDAC inhibitor: this mean that there’s a synergistic effect between increase of acetylation and the activation of demethylation. For this reason, the supplement of SAMe is not recommended.

The vitamins of group B are used to carrier and bind methyl group, then supplementation of high amount of B vitamins is not recommended if the increase of demethylation is wanted.

The Zn²⁺ ion is he natural cofactor of HDAC, then the uses of Zn²⁺ supplements may increase their activities.

I hope that a combination of the induction of gene’s plasticity and the antagonism to serotonin receptors may help to recover from the disease.  

[1] Mechanisms of control of 5-HT neurons are:

• self-inhibition through 5-HT_1A autoreceptors (activation of these receptors by 5-HT diminish neuronal firing and produce a negative feedback regulation of transmitter release)
• 5-HT_1B/1D receptors, located on nerve terminals, respond to 5-HT released locally in the terminal fields inhibiting further transmitter release.

 These 2 mechanisms ensure tight feedback control of the activity of serotonergic neurons and of terminal 5-HT release.
Thus, a prolonged treatment whit ssri may lead to a reduction of binding site for serotonin on SERT, then its ability to reuptake serotonin is chronically diminished.
Chronic administration of selective serotonin reuptake inhibitors (but not amitriptyline) results in the desensitization of 5-HT_1A somatodendritic autoreceptor function in the dorsal raphe but not in hippocampus, and also results in the desensitization of physiological responses mediated by postsynaptic 5-HT_1A receptors.
In general, changes in 5-HT_1A receptor number have not been observed following chronic administration of antidepressants.
A study (Julie G Hensler, 2002) ipotizes that the desensitization of somatodendritic 5-HT_1A autoreceptors in the dorsal and median raphe following chronic SSRI treatment do not appear to be mediated by changes in 5-HT_1A receptor binding but may be due to a reduced capacity of the 5-HT_1A receptor to activate G protein. By contrast, no significant change in postsynaptic 5-HT_1A binding following chronic antidepressant treatment.
 

[2] Newton SS, Duman RS (August 2006). “Chromatin remodeling: a novel mechanism of psychotropic drug action”. Mol. Pharmacol. 70 (2)
 

[3] Safarinejad MR, Sperm DNA Damage and Semen Quality Impairment After Treatment With Selective Serotonin Reuptake Inhibitors Detected Using Semen Analysis and Sperm Chromatin Structure Assay
 

[4] The genetics of selective serotonin reuptake inhibitors, Kroeze
 

[5] Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology, Csoka
 

[6] Faure C, Mnie-Filali O, Haddjeri N (February 2006). “Long-term adaptive changes induced by serotonergic antidepressant drugs”. Expert Rev Neurother
 

[7] Palotás M, Palotás A, Puskás LG, et al. (December 2004). “Gene expression profile analysis of the rat cortex following treatment with imipramine and citalopram”. Int. J. Neuropsychopharmacol
 

[8] Kálmán J, Palotás A, Juhász A, et al. (November 2005). “Impact of venlafaxine on gene expression profile in lymphocytes of the elderly with major depression–evolution of antidepressants and the role of the “neuro-immune” system”.
 

[9] Yamada M, Yamada M, Higuchi T (July 2005). “Antidepressant-elicited changes in gene expression: remodeling of neuronal circuits as a new hypothesis for drug efficacy”. Prog. Neuropsychopharmacol. Biol. Psychiatry
 

[10] Boehm C, Newrzella D, Herberger S, Schramm N, Eisenhardt G, Schenk V, Sonntag-Buck V, Sorgenfrei O (2006). “Effects of antidepressant treatment on gene expression profile in mouse brain: cell type-specific transcription profiling using laser microdissection and microarray analysis”.

[11] RGFP109, a histone deacetylase inhibitor attenuates L-DOPA-induced dyskinesia in the MPTP-lesioned marmoset: a proof-of-concept study, Johnston TH

[12] Histone deacetylase inhibitors reverse CpG methylation by regulating DNMT1 through ERK signaling, Sarkar S

[13] Green tea polyphenols for prostate cancer chemoprevention: A translational perspective J.J. Johnson

[14] Flavonoids Influence Epigenetic-Modifying Enzyme Activity: Structure-Function Relationships and the Therapeutic Potential for Cancer Gilbert, E.R.; Liu, D.

[15] Epigenetic activities of flavonoids in the prevention and treatment of cancer, Christian Busch

[16] http://link.springer...z/fulltext.html

[17] Epigenome, Cancer Prevention and Flavonoids and Curcumin, Višnja Stepanić

[18] Dietary Polyphenols May Affect DNA Methylation, Mingzhu Fang

[19] Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain disease, Ronald Ross Watson,Victor R. Preedy

[20] Mechanisms for the Inhibition of DNA Methyltransferases by Tea Catechins and Bioflavonoids, Won Jun Lee

[21] The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells, Zhu WG

[22] Epigenetic changes induced by curcumin and other natural compounds, Simone Reuter

[23] Green Tea Polyphenols in drug discovery - a success or failure?, Thomas J. Smith

[24] Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E, Chow HH

[25] Molecular targets of (-)-epigallocatechin-3-gallate (EGCG): specificity and interaction with membrane lipid rafts, Patra SK

[26] Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation, Dong E

[27] Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII, D'Addario C.

 

[28] Valproate induces DNA demethylation in nuclear extracts from adult mouse brain, Erbo Don

 

[Blake Thacker]

Is the MAOI Parnate free from Permanent Post SSRI Sexual disorder? or does Parnate, Nardil and Marplan cause it just as much as SSRI/SNRI's?