Posted by SLS on May 20, 2009, at 5:33:24
In reply to Re: Why do SSRIs SNRIs affect libido?, posted by desolationrower on May 19, 2009, at 11:35:46
> > I thought Nefazodone and Cyproheptadine were 5ht2a antagonists? Is that the receptor that kills libido?
>
> its probably the most inmportant one
>
> > also for the poster, genereic Nefazodone (Serzone) IS still available. Its made by Teva pharmaceuticals. So you could always get back on that if you had success with it.
>
> if your doc will prescribe, mine was scared of it
>
> -d/r
What about 5-HT2c receptors being acutely overstimulated and leading to their long-term downregulation? At first, there might even be an accommodation of the postsynaptic neuron due to hyperpolarization that would prevent it from firing. This would produce a reduction of libido and erectile function acutely. Chronic sexual dysfunction would then be the result of downregulation. However, one would expect a brief window of increased sexual activity were this true.5-HT2b overstimulation seems to suppress sexual behavior in rats acutely. This is another route through which SRIs can reduce sexual function.
Two studies that might be applicable:
1. Interesting study using mCPP as a 5-HT2c agonist that produces acute increases in libido.2. Demonstration that 5-HT2c agonists can produce an acute antidepressant effect. It also demonstrates that chronic administration of higher dosages produces a decrease in libido.
- Scott
*****************************************
1.
Pharmacol Biochem Behav. 2008 Feb;88(4):367-73. Epub 2007 Sep 18.Click here to read Links
Ejaculatory response induced by a 5-HT2 receptor agonist m-CPP in rats: differential roles of 5-HT2 receptor subtypes.
Yonezawa A, Yoshizumi M, Ebiko M, Ise SN, Watanabe C, Mizoguchi H, Kimura Y, Sakurada S.Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. [email protected]
It has been reported that systemic administration of m-CPP (1-[3-chlorophenyl] piperazine hydrochloride), a 5-HT(2) receptor agonist, produces a 5-HT(2C) receptor-mediated penile erections and self-grooming in rats. In the present study, we examined the ability of m-CPP to induce ejaculation in rats and determined which 5-HT(2) receptor subtypes may be involved in the m-CPP-induced ejaculation. The ejaculatory response was assessed by weighing the seminal materials accumulated over 30 min. In Experiment 1, systemic administration of m-CPP (0.1-3.0 mg/kg, i.p.) produced a dose-dependent increase in both the incidence of ejaculation and the weight of the seminal materials. The inverted U-shaped dose-response effects of m-CPP on penile erection and genital grooming were also observed, with maximum effects at 0.6 mg/kg. Pretreatment with SB242084 (0.1 and 0.3 mg/kg, i.p.), a selective 5-HT(2C) receptor antagonist, dose-dependently attenuated the ejaculatory response induced by m-CPP (3.0 mg/kg). The proejaculatory effect of m-CPP was also attenuated by ketanserin (0.3 and 1.0 mg/kg, i.p.), a 5-HT(2A) receptor antagonist, whereas SB204741 (0.1 and 0.3 mg/kg, i.p.), a selective 5-HT(2B) receptor antagonist, significantly potentiated the m-CPP-induced ejaculatory response. Penile erection and genital grooming induced by m-CPP (0.3 mg/kg, i.p.) was only blocked by SB242084. In Experiment 2 (termed as corset test), in rats fitted with a corset at the thoracic level to prevent the loss of seminal materials by genital grooming, the proejaculatory effect of m-CPP was more efficiently detected than in the non-fitted animals: the ED(50) value for inducing ejaculation was reduced to less than 50% of the ED(50) in non-fitted animals. In this test, the proejaculatory effect of m-CPP (0.6 mg/kg, i.p.) was completely blocked by SB242084 (0.3 mg/kg, i.p.), whereas ketanserin (0.3 mg/kg, i.p.) or SB204741 (0.3 mg/kg, i.p.) did not affect the m-CPP -induced ejaculation. From these observations, it is suggested that the 5-HT(2) receptor agonist m-CPP at low doses (0.3-1.0 mg/kg) possesses the proejaculatory as well as proerectile effects in rats that are primarily associated with the activation of 5-HT(2C) receptors, and that the activation of 5-HT2B receptors may produce an inhibitory effect on ejaculation induced by a high dose (3.0 mg/kg) of m-CPP. Furthermore, the results of the present study also indicate that the corset test employed in this study may be useful for detecting the proejaculatory effect of the compounds.
*****************************************
2.
Psychopharmacology (Berl). 2007 Jun;192(2):159-70. Epub 2007 Feb 13.Click here to read Links
Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents.
Rosenzweig-Lipson S, Sabb A, Stack G, Mitchell P, Lucki I, Malberg JE, Grauer S, Brennan J, Cryan JF, Sukoff Rizzo SJ, Dunlop J, Barrett JE, Marquis KL.Discovery Neuroscience, Wyeth Research, CN-8000, Princeton, NJ 08543, USA. [email protected]
RATIONALE: Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of SSRIs. OBJECTIVE: The present studies were conducted to evaluate the effects of the novel 5-HT2C receptor agonist WAY-163909 in animal models of antidepressant activity (forced swim test (FST), resident-intruder, olfactory bulbectomy (BULB)), in a schedule-induced polydipsia (SIP) model of obsessive-compulsive disorder and in a model for evaluating sexual dysfunction. RESULTS: WAY-163909 (10 mg/kg, i.p. or s.c.) decreased immobility time in Wistar-Kyoto rats in the FST, effects that were reversed by the 5-HT2C/2B receptor antagonist SB 206553. Moreover, in Sprague-Dawley rats, the profile of WAY-163909 (decreased immobility, increased swimming) in the FST was comparable to the effects of SSRIs. Acute treatment with WAY-163909 (0.33 mg/kg, s.c.) decreased rodent aggression at doses lower than those required for decreasing total behavior. Administration of WAY-163909 (3 mg/kg, i.p.) for 5 or 21 days decreased the BULB-induced hyperactivity in rats. Additionally, acute administration of WAY-163909 (3 mg/kg, i.p.) decreased adjunctive drinking in a SIP model. The effects of WAY-163909 were reversed by the 5-HT(2C/2B) receptor antagonist SB 206553 and the selective 5-HT2C receptor antagonist SB 242084. Chronic administration of WAY-163909 produced deficits in sexual function at doses higher (10 mg/kg, i.p.) than those required for antidepressant-like effects in the BULB model. CONCLUSIONS: Taken together, these results demonstrate that the novel 5-HT2C receptor agonist WAY-163909 produces rapid onset antidepressant-like effects in animal models and may be a novel treatment for depression.
poster:SLS
thread:879556
URL: http://www.dr-bob.org/babble/neuro/20090129/msgs/896759.html