6 replies to this topic

[IndyX]

Currently I'm recovering from ssri's, I'm trying lot of stuff - mainly high doses of ginkgo biloba and shilajit - but also other moderately dosed herbs like panax ginseng, ashwagandha, forskolin, boswellia, pomegranate extract, curcumin and pycnogenol.

 

I believe my nitric oxide synthase is suppressed, because arginine & cytruline do absolutely nothing for erections like they used to. It's about erections in the first place - so help in that matter is much appreciated.

 

I've tried piracetam and DAA - didn't notice spectacular effects. I'm going into piracetam again coupled with somewhat more curcumin.

 

Any advices?

[gamesguru]

Most of those supplements are harmless; even the SSRIs, at low dose and not used prolongedly.

 

Salix alba^[1]

Low sat fat^[2]

Exercise^{[3], [4]}

 

also, sometimes it's undesirable to induce iNOS

Regulation of the expression of inducible nitric oxide synthase

 

Nitric oxide (NO), generated by the inducible isoform of nitric oxide synthase (iNOS), has been described to have beneficial microbicidal, antiviral, antiparasital, immunomodulatory, and antitumoral effects. However, aberrant iNOS induction at the wrong place or at the wrong time has detrimental consequences and seems to be involved in the pathophysiology of several human diseases [including herpes simplex 1]. 

iNOS expression can be induced in many cell types with suitable agents such as bacterial lipopolysaccharides (LPS), cytokines, and other compounds. Pathways resulting in the induction of iNOS expression may vary in different cells or different species.

Activation of the transcription factors NF-kappaB and STAT-1alpha, and thereby activation of the iNOS promoter, seems to be an essential step for iNOS induction in most cells. However, at least in the human system, also post-transcriptional mechanism are critically involved in the regulation of iNOS expression. The induction of iNOS can be inhibited by a wide variety of immunomodulatory compounds acting at the transcriptional levels and/or post-transcriptionally [including green tea]

Edited by gamesguru, 08 September 2015 - 12:59 PM.

[Area-1255]

Currently I'm recovering from ssri's, I'm trying lot of stuff - mainly high doses of ginkgo biloba and shilajit - but also other moderately dosed herbs like panax ginseng, ashwagandha, forskolin, boswellia, pomegranate extract, curcumin and pycnogenol.

I believe my nitric oxide synthase is suppressed, because arginine & cytruline do absolutely nothing for erections like they used to. It's about erections in the first place - so help in that matter is much appreciated.

I've tried piracetam and DAA - didn't notice spectacular effects. I'm going into piracetam again coupled with somewhat more curcumin.

Any advices?

IndyX  - that's exactly how it is with SSRI's - you are on the right track there bud. 

 

There a number of pathways involved in NOS..but if you are desensitized by the SSRI - then you may end up needing to block the post-synaptic 1A receptors...you may also need to antagonize the 2C receptors...however, a couple methods to start with - you could use naltrexone (25 mg - 50 mg / day) coupled with something that acts directly on the dopamine systems...perhaps an agonist or L-DOPA. You could also try nefiracetam combined with DAA or DAA + Sarcosine and a glycine site agonist...

 

So start with Test Force II with has a glycine reuptake inhibitor (Sarcosine) + DAA in it..this makes the DAA work better and longer..then you can use Ashwagandha as a direct glycine site agonist. 

 

Naltrexone can be added as you see fit to both TF II and Ashwagandha. 

 

 

Psychoneuroendocrinology. 1989;14(1-2):103-11.

Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.

Fabbri A1, Jannini EA, Gnessi L, Moretti C, Ulisse S, Franzese A, Lazzari R, Fraioli F, Frajese G, Isidori A.

Author information

 

Abstract

In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.

PMID:   2543996   [PubMed - indexed for MEDLINE]  

 

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Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1722-6.

beta-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release.

Faletti AG1, Mastronardi CA, Lomniczi A, Seilicovich A, Gimeno M, McCann SM, Rettori V.

Author information

 

Abstract

beta-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating mu-opiate receptors, thereby inhibiting secretion of LH. LHRH release is controlled by release of nitric oxide from nitricoxidergic (NOergic) neurons in the basal tuberal hypothalamus. To determine whether beta-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with beta-endorphin (10(-8) M). beta-Endorphin decreased basal secretion of LHRH, and significantly inhibited the release of prostaglandin E2 (PGE2), a known stimulant of LHRH release. Incubation of MBH with beta-endorphin at various concentrations (10(-9)-10(-6) M) in vitro decreased the activity of NO synthase (NOS) (measured by the conversion of [14C]arginine to labeled citrulline). Conversely, the activity of NOS was increased by the mu-receptor antagonist, naltrexone (10(-8) M). Not only was the inhibitory action of beta-endorphin on LHRH and PGE2 release blocked by naltrexone (10(-8) M), but it increased NOS activity and LHRH and PGE2 release. beta-Endorphin also stimulated gamma-aminobutyric acid (GABA) release. Because GABA inhibits both nitroprusside (NP-induced PGE2 and LHRH release by blocking the activation of cyclooxygenase by NO, this is another mechanism by which beta-endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that beta-endorphin stimulates mu-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. beta-Endorphin also blocks the action of NO on PGE2 release and, consequently, on LHRH release, by stimulating GABAergic inhibitory input to LHRH terminals that blocks NO-induced activation of cyclooxygenase and consequent PGE2 secretion.

PMID:   9990091   [PubMed - indexed for MEDLINE]    PMCID:   PMC15573     Free PMC Article

 

Gen Pharmacol. 1997 Aug;29(2):223-7.

Time course of the changes in central nitric oxide synthase activity following chronic treatment with morphine in the mouse: reversal by naltrexone.

Kumar S1, Bhargava HN.

Author information

 

Abstract

1. The time course of the effect of chronic administration of morphine on the activity of nitric oxide synthase (NOS) in the brain regions and spinal cord of the mouse was determined. The effect of naltrexone by itself on the NOS activity and that induced by morphine also were determined. 2. Male Swiss Webster mice were implanted subcutaneously with a pellet containing 25 mg of morphine free base for 4 days. Placebo pellet implanted mice served as controls. 3. Twenty-four hours after treatment with morphine, NOS activity decreased in the cerebellum, midbrain, cortex and remainder of the brain as well as in the spinal cord. Forty-eight and 72 hr after the treatment with morphine, NOS activity increased in the cerebellum and cortex, but no change was observed in the other brain regions and spinal cord. Twenty-four hours after morphine pellet removal (withdrawal), NOS activity in all brain regions and the spinal cord has returned to normal. 4. Implantation of a pellet containing 10 mg of naltrexone did not alter NOS activity in any brain region or spinal cord for 24, 48 and 72 hr or 24 hr after removal of the pellet. 5. Implantation of a naltrexone pellet in conjunction with a morphine pellet blocked the changes in NOS activity in the brain region and spinal cord induced by morphine. 6. It is concluded that the initial decrease in NOS activity by morphine may be related to enhanced motor activity, whereas the increase in NOS activity in certain brain regions may be associated with tolerance-physical dependence development. Additionally, the changes in central NOS activity by morphine appear to be mediated by opioid receptors because they were blocked by concurrent treatment with naltrexone.

PMID:   9251903   [PubMed - indexed for MEDLINE]

Endogenous Opioids Regulate the Expression of Inducible Nitric Oxide Synthase by Splenocytes1

 

 

 

Potentiation of NMDA Receptors by Withania somnifera on Hippocampal CA1 Pyramidal Neurons

Janardhan Prasad Bhattarai

• Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea

Soo Joung Park

• Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea

Seong Kyu Han

• Correspondence to: Dr. Seong Kyu Han, Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju 561-756, Korea. Tel: (+82) 63-270-4030, Fax: (+82) 63-270-4028.
• Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea

 

In Ayurveda,Withania somnifera (WS) is used as a medicine to maintain mental and physical health as well as to enhance memory. In this study, the methanolic extract of WS(mWS) was tested for its electrical influence on hippocampal CA1 pyramidal neurons using a patch clamp technique. In current clamp mode under a high chloride pipette solution, mWS (400 ng/μl) induced remarkable membrane depolarization (9.75 ± 2.54 mV, n = 6) of CA1 neurons. The mWS-induced depolarization was dose-dependent, reproducible, and persistent in the presence of 0.5 μM tetrodotoxin (TTX, 10.17 ± 0.04 mV, n = 6). In voltage clamp mode (holding potential = -60 mV), mWS induced a dose-dependent non-desensitizing inward current that persisted in the presence of TTX (0.5 μM), suggesting that the response induced by mWS was purely a postsynaptic event. Interestingly, these inward currents were partially blocked by strychnine, a glycine receptor blocker. Further, mWS potentiated the NMDA response in hippocampal CA1 neurons at low concentrations. Overall, these results suggest that there are compounds in WS with possible glycine mimetic activities, which may be potential targets for inducing memory consolidation in hippocampal CA1 neurons.

Keywords: Withania somnifera ; Hippocampal CA1 Neurons; NMDA; Whole Cell Patch Clamp Technique

Read More: http://www.worldscie...192415X13500365

[IndyX]

Thanks for reply Area   How about Low Dose Naltrexone?  I'm forced to try it (or even use long term) due to high autoantibodies (Hashimoto's). God..it's so fuckin complex..well, also fascinating

[Area-1255]

Thanks for reply Area   How about Low Dose Naltrexone?  I'm forced to try it (or even use long term) due to high autoantibodies (Hashimoto's). God..it's so fuckin complex..well, also fascinating

LDN will likely only raise beta-endorphin; your best bet is higher doses as that is the amount used in E.D patients and even in those with diminished testosterone secretion...you may want to get hormones checked as well BTW.

 

Mianserin might help if it is available over there..I think it is in Poland?

 

WAY 100 635 is a powerful 1A antagonist with D4 agonist properties but it is ridiculously expensive.

 

Read this thread brother. 

http://www.longecity.org/forum/topic/73458-natural-5-ht1a-agonistsantagonists-pssdand-cognitive-function/

 

---->  http://tht.co/product/way100635/ 

 

https://www.reddit.com/r/PSSD/comments/3dg8p4/5ht1a_antagonist_way_100_635_now_available_may/

 

 

Br J Pharmacol. 2000 Aug;130(8):1853-8.

Serotonin inhibition of the NMDA receptor/nitric oxide/cyclic GMP pathway in human neocortex slices: involvement of 5-HT(2C) and 5-HT(1A) receptors.

Maura G1, Marcoli M, Pepicelli O, Rosu C, Viola C, Raiteri M.

Author information

 

Abstract

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. The cyclic GMP elevation produced by 100 microM NMDA was blocked by 100 microM of the NO synthase inhibitor N(G)-nitro-L-arginine (L-NOARG) or by 10 microM of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha] quinoxaline-1-one (ODQ). The NMDA effect was prevented by 5-HT or by the 5-HT(2) agonist (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)-DOI; EC(50)=22 nM). The (+/-)-DOI inhibition was insensitive to the 5-HT(2A) receptor antagonist MDL 100907 or the 5-HT(2B) antagonist rauwolscine; it was largely prevented by 1 microM of the non-selective 5-HT(2C) antagonists mesulergine (5-HT(2A,B,C)), ketanserin (5-HT(2A,C)) or SB 200646A (5-HT(2B,C)); it was completely abolished by 0.1 microM of the selective 5-HT(2C) receptor antagonist SB 242084. The NMDA-induced cyclic GMP elevation also was potently inhibited by the selective 5-HT(2C) agonist RO 60-0175 and by the antidepressant trazodone, both added at 1 microM, in an SB 242084-sensitive manner. Finally, the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 1 microM) inhibited the NMDA-evoked cyclic GMP response, an effect blocked by the selective 5-HT(1A) receptor antagonist WAY 100635. In conclusion, the NMDA receptor/NO/cyclic GMP pathway in human neocortex slices can be potently inhibited by activation of 5-HT(2C) or 5-HT(1A) receptors.

PMID:   10952674   [PubMed - indexed for MEDLINE]    PMCID:   PMC1572268     Free PMC Article

 

Edited by Area-1255, 12 September 2015 - 08:09 PM.

[IndyX]

I keep way 100 635 in my mind, but more like a last resort. Minaserin is available in Poland, but I'm somewhat skeptical of both of them. I want that stuff going on auto. Agonizing/antagonizing receptors manually could do more harm than good in the long term because of delayed recovery (if it's true?), unless psyche, thoughts, "yes, I can" and stuff, which constantly re-plasticize brain (at least I want to believe).

 

Things are getting slowly (however can't say steadily) better. I'll try some quasi-green stuff first, like ginkgo, shilajit, curcumin, inositol and god damn positive thinking. Naltrexone would be my next choice for sure - thanks for clearly pointing that out.

 

Hormones are fucked up. Last time I chcecked Testosteron and LH were low-low-reference. If they still there, I'll add Tamoxifen, then Naltrexone, get rid of Tamox and re-chceck.

[Area-1255]

I keep way 100 635 in my mind, but more like a last resort. Minaserin is available in Poland, but I'm somewhat skeptical of both of them. I want that stuff going on auto. Agonizing/antagonizing receptors manually could do more harm than good in the long term because of delayed recovery (if it's true?), unless psyche, thoughts, "yes, I can" and stuff, which constantly re-plasticize brain (at least I want to believe).

 

Things are getting slowly (however can't say steadily) better. I'll try some quasi-green stuff first, like ginkgo, shilajit, curcumin, inositol and god damn positive thinking. Naltrexone would be my next choice for sure - thanks for clearly pointing that out.

 

Hormones are fucked up. Last time I chcecked Testosteron and LH were low-low-reference. If they still there, I'll add Tamoxifen, then Naltrexone, get rid of Tamox and re-chceck.

Naltrexone will help raise LHRH and testosterone as well...tamox could help along with it.

Speed up the effects.

Your serotonin autoreceptors of the 1A type are desensitized leading to a flood of serotonin on all other receptors including the POST-SYNAPTIC 1A receptors...the post-synaptic ones inhibit nitric oxide and glutamate as well as a lot of second messengers so they end up messing up a lot of things when over active...e.g heart rate, libido, awareness , memory

 

 

If things are slowly getting better - I don't think your case is awful , but yet, keep positive thinking..anxiety and negative thoughts only hinder progress. 

 

Read my article. http://area1255.blog...on-of-data.html