3 replies to this topic

[medievil]

Gen Pharmacol. 1983;14(5):475-9.
Inhibition of adenosine uptake into rat brain synaptosomes by prostaglandins, benzodiazepines and other centrally active compounds.

Phillis JW, Wu PH, Coffin VL.

Abstract

A number of compounds have been tested for their abilities to inhibit the rapid uptake of adenosine by rat cerebral cortical synaptosomes. Prostaglandins PGI2, PGA2, and PGE1 and PGE2 were potent inhibitors of adenosine uptake with IC20 values in the 10(-7) M-10(-6) M range. PGA1, PGD2 and PGF2 alpha also inhibited uptake but were less active. The benzodiazepine antagonist Ro 15-1788 inhibited adenosine uptake and failed to antagonize the effects of diazepam. Another antagonist, ethyl-beta-carboline-3-carboxylate, was a weak inhibitor of adenosine uptake. Ro 5-4864, the so-called peripheral benzodiazepine ligand, inhibited adenosine uptake. Hydroxyzine and tracazolate, two anxiolytic agents, inhibited uptake as did flunarizine, a coronary vasodilator. Two calmodulin antagonists, W7 and R 24571, were effective inhibitors of adenosine uptake. Their IC50 values were comparable to those at which they have been demonstrated to inhibit calmodulin-mediated reactions in other systems. These observations suggest that adenosine uptake may be a calmodulin-regulated process.

Adenosing reuptake inhibitor

Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine.
[My paper] J O'Sullivan , M I O'Sullivan , K E Tipton , G Davey

The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) were studied. Hydroxyzine was found to be a competitive inhibitor of MAO-B (Ki - 38 microM), whereas it had a low potency towards MAO-A (IC50 > 630 microM). Although it was a relatively potent competitive inhibitor of bovine plasma SSAO (Ki approximately 1.5 microM), it was a weak inhibitor of the membrane-bound form of the enzyme from bovine lung (IC50 approximately 1 mM). These findings extend our knowledge of the drug binding capabilities of the amine oxidases and suggest that these interactions may contribute to the complex actions of this drug.

MAOBI

Pharmacology

Hydroxyzine's predominant mechanism of action is as a potent H₁ receptor inverse agonist (K_i = 2 nM).^{[20][21][22][23]} Unlike most other first-generation antihistamines, it has negligible affinity for the mACh receptors (K_i = >10,000 nM) and therefore does not produce any clinically significant anticholinergic effects.^{[21][22][23][24][25]} In addition to its antihistamine activity, hydroxyzine has also been shown to act as a 5-HT_2A (K_i = ~50 nM), D₂ (K_i = 378 nM), and α₁-adrenergic (K_i = ~300 nM ) receptor antagonist.^[21][22][24]
Hydroxyzine's antiserotonergic effects likely underlie its usefulness as an anxiolytic,^[26][27] as other antihistamines without such properties are not effective in the treatment of anxiety.^[27]

It probably does alot more, ill return to this thread.

[brainslugged]

I ordered some of this from ADC a month or so ago and unfortunately paid by mailing a check (I wish I would have know what a bad decision that was going to be). But the check still hasn't even gone through, so I have no idea when I will actually get the medicine or if I will maybe have to re-order. You can buy it from ADC yourself if you want to try it out. It is pretty cheap, and if you buy it with other stuff, you can get a pretty good deal since the base shipping cost is the biggest expense on ADC.

It is a very interesting drug, and I think that since it is antiserotonergic it actually may have great effect on some anxiety disorders or people with high harm-avoidance.
http://www.ncbi.nlm..../pubmed/3809156

Evidence suggests that variation in each dimension is strongly correlated with activity in a specific central monoaminergic pathway: novelty seeking with low basal dopaminergic activity, harm avoidance with high serotonergic activity, and reward dependence with low basal noradrenergic activity.

Of course, I don't know how trustworthy that article is since it is just an analysis and I don't see any evidence support provided by it. I suppose it's worth a try, though.

The MAOBI properties are very interesting, as are the Adenosing reuptake inhibitor properties, and I am wondering if it could then be used to potentate stimulants while also reducing negative side effects and neurotoxicity, or at least relieve side effects without decreasing the effectiveness of the stimulants.

It looks like it could be a good mild antipsychotic/anxiolytic that doesn't significantly impair functioning like benzos do. It's metabolite/derivative, cetirizine (Zyrtec), is hands down my favorite medicine for allergies, so I am hopeful.

[medievil]

Isnt it metabolite loratadine?

Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines.

Soule BP, Simone NL, DeGraff WG, Choudhuri R, Cook JA, Mitchell JB.

Source

Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. souleb@mail.nih.gov

Abstract


BACKGROUND:

The histamine receptor-1 (H1)-antagonist, loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma (HT29).
METHODS:

Cells were treated with several doses of loratadine at several time points before and after exposure to radiation. Radiation dose modifying factors (DMF) were determined using full radiation dose response survival curves. Cell cycle phase was determined by flow cytometry and the expression of the cell cycle-associated proteins Chk1, pChk1(ser345), and Cyclin B was analyzed by western blot.
RESULTS:

Loratadine pre-treatment of exponentially growing cells (75 microM, 24 hours) increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95. However, treatment of plateau phase cells also yielded a DMF of 1.3 suggesting that mechanisms other than cell cycle arrest also contribute to loratadine-mediated radiation modification. Like irradiation, loratadine initially induced G2/M arrest and activation of the cell-cycle associated protein Chk1 to pChk1(ser345), however a subsequent decrease in expression of total Chk1 and Cyclin B correlated with abrogation of the G2/M checkpoint. Analysis of DNA repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA damage in loratadine-treated cells in addition to enhanced radiation-induced damage. Taken together, these data suggest that the observed effects of loratadine are multifactorial in that loratadine 1) directly damages DNA, 2) activates Chk1 thereby promoting G2/M arrest making cells more susceptible to radiation-induced DNA damage and, 3) downregulates total Chk1 and Cyclin B abrogating the radiation-induced G2/M checkpoint and allowing cells to re-enter the cell cycle despite the persistence of damaged DNA.
CONCLUSIONS:

Given this unique possible mechanism of action, loratadine has potential as a chemotherapeutic agent and as a modifier of radiation responsiveness in the treatment of cancer and, as such, may warrant further clinical evaluation.

like all antihistamines it has something unigue, but damn its shit to go trough to them all and disover it hahaha

Loratadine does cross the BBB

Clin Neurophysiol. 2012 Apr;123(4):780-6. doi: 10.1016/j.clinph.2011.07.046. Epub 2011 Aug 30.
Low dosage promethazine and loratadine negatively affect neuromotor function.

Kavanagh JJ, Grant GD, Anoopkumar-Dukie S.

Source

School of Physiotherapy and Exercise Science, Griffith University, Gold Coast, Australia. j.kavanagh@griffith.edu.au

Abstract


OBJECTIVES:

Determine how the sedating antihistamine promethazine and non-sedating antihistamine loratadine at a dose of 10mg influence voluntary and involuntary motor processes in the hours following ingestion and the morning after ingestion.
METHODS:

Eight healthy young adults were recruited into a human double-blind, placebo-controlled, three-way crossover study. Neuromotor function was examined using a battery of controlled reaction time, postural tremor, and heart rate variability measures. Neuromotor function was assessed 4 times for each of the promethazine, loratadine and placebo interventions; pre-ingestion, 1h post-ingestion, 2h post-ingestion, and the following day.
RESULTS:

Self-perceived levels of drowsiness increased only after ingestion of promethazine. However, both antihistamines had negative effects on simple reaction time, choice reaction time, the RMS and peak power amplitude of postural tremor, and autonomic cardiac regulation.
CONCLUSIONS:

The presence of selective neuromotor deficits following ingestion of promethazine and loratadine suggest that sedating and non-sedating antihistamines alter neuromotor function. It is possible that the H(1) antagonists used in this study have antimuscarinic effects, which may impact on the central dopaminergic system that plays a role in modulating several CNS processes associated with movement.
SIGNIFICANCE:

Antihistamines are one of the most commonly procured over-the-counter medications. The current study suggests that taking non-sedating antihistamines to avoid the adverse drug reaction of drowsiness may not avoid unwanted motor control side-effects.
Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jun;29(5):754-6.
An open-label series using loratadine for the treatment of sexual dysfunction associated with selective serotonin reuptake inhibitors.

Aukst-Margetić B, Margetić B.

Source

Neuropsychiatric Hospital Dr. Ivan Barbot Vinogradska 55, Popovaca 44317, Croatia. branka.aukst-margetic@zg.htnet.hr

Abstract


OBJECTIVE:

To assess the impact of loratadine as an add-on treatment of erectile dysfunctions associated with selective serotonin reuptake inhibitors (SSRIs).
METHODS:

Nine patients diagnosed as major depressive disorder (MDD), with erectile dysfunction associated with the administration of SSRIs, completed a 2-week trial of loratadine in the dose of 10 mg/day. The International Index of Erectile Function Five (IIEF-5) was used as an assessment measure for diagnosing the presence and severity of erectile dysfunction. The 17-item Hamilton Rating Scale for Depression (HAM-D) was administered for screening the potential impact of depressive symptoms.
RESULTS:

Baseline mean S.D.+/-IIEF-5 scores were 10.33+/-4.55 (range 5-20) and week 2 mean+/-S.D. IIEF-5 was 14.44+/-3.84 (range 10-22). Subjects had statistically significant improvement in their erectile functions on the IIEF-5 (t = -8.485; df = 8; p = 0.000) and 55% reported subjective improvement of the erectile function. No significant changes on HAM-D 17 scores were registered. Baseline mean S.D. scores were 13.66+/-2.29 (range 10-17) and week 2 mean S.D. was 13.11+/-1.96 (range 10-16) (t = 1.47; df = 8; p = 0.179).
CONCLUSION:

Our findings suggest the possible role of loratadine in the treatment of SSRI-associated sexual dysfunction. They are promising, but preliminary. Thus they should be replicated in a longer large-scale, double-blind, placebo-controlled trial.

It should be simular to hydroxyzine as its a metabolite of it so a potential anxiolytic, any experiences here? also anyone has full binding profile?

[medievil]

takes shitload work going trough all over pubmed with just one antihistamine or whatever, but discovered some shit that could have tremendous therapeutic potential so its worth it, its like digging trough the amazon to find novel cures.

Ive said it many times we can allready cure pretty much everything, except the cures are hidden or are rc's, or still need to be synthed thats all not impossible to do.