Posted by Dave001 on July 20, 2004, at 1:54:13
In reply to SSRI With the Least Sexual Side Effects, posted by Lex Luthor on July 19, 2004, at 15:30:26
> I wonder which one is it.
>
> Any information or opinions, anyone?From a theoretical standpoint based upon the mechanisms by which SSRIs are known to induce sexual dysfunction and the data currently available in the scientific literature, I would say Celexa (or Lexapro). Paxil looks the worst on paper. Much of my speculation is based on effect of the various SSRIs on nitric oxide (NO). Citalopram is the only SSRI for which I've found evidence of NOT adversely affecting NO. I've included several abstracts below which support this claim.
BTW, for those unfamiliar with the biological role of NO, here is a quick point to help put some of the above in perspective: sildenafil (Viagra) works by locally increasing the level of NO. It does not directly mimic NO but increases it indirectly by inhibiting the breakdown of cyclic GMP.
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Differential effects of serotonin reuptake inhibitors on erectile
responses, NO-production, and neuronal NO synthase expression in rat
corpus cavernosum tissue.Br J Pharmacol 2001 Nov;134(6):1190-4 (ISSN: 0007-1188)
Angulo J; Peiro C; Sanchez-Ferrer CF; Gabancho S; Cuevas P; Gupta S;
Saenz de Tejada I
Fundacion para la Investigacion y el Desarrollo en Andrologia,
Department de Investigacion, Hospital Ramon y Cajal, Madrid, Spain.Increased incidence of impotence is associated with some selective
serotonin-reuptake-inhibitors (SSRIs), but the pathophysiological
mechanism is unknown. Paroxetine and citalopram are extensively used
SSRIs, but only paroxetine has been shown to inhibit nitric oxide
synthase (NOS) activity. NO is a key mediator of penile erection. Thus,
the aim of this study was to determine the effects of paroxetine and
citalopram on erectile function and NO production, in a rat model.
Application of cavernosal nerve electrical stimulation produced
frequency-related intracavernosal pressure (ICP) increases, which were
inhibited by the NOS inhibitor, N(G)-nitro-L-arginine (0.3 mg x kg(-1)).
Acute or chronic (2 weeks) paroxetine-treatment (10 mg x kg(-1)) reduced
ICP-responses, while citalopram did not. Paroxetine, but not citalopram,
significantly reduced nitrite+nitrate plasma levels by 61.4% and
inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after
chronic treatment. The results show that paroxetine inhibits erectile
responses in rats. We propose that this effect is due to reduced NO
production and nNOS expression.
---------------------------------------------------------------J Pharmacol Exp Ther. 2004 Jul;310(1):141-9. Epub 2004 Mar 19.
Mechanisms for the inhibition of genital vascular responses by
antidepressants in a female rabbit model.Angulo J, Cuevas P, Cuevas B, Gupta S, De Tejada IS.
Antonio Robles, 4-9C, 28034 Madrid, Spain. isdtejada@terra.es
Vaginal and clitoral vasodilator responses (genital vascular responses;
GVRs) to pelvic nerve electrical stimulation in female rabbits were
measured by laser Doppler flow needle probes. The intravenous
administration of various treatments was evaluated. GVRs were attenuated
by a nitric-oxide synthase inhibitor (48.5 and 51.8% of control at 8 Hz
in the vagina and clitoris, respectively) and norepinephrine (NE) (78.5
and 61.5%), whereas serotonin (5-HT) had no inhibitory effect. The
selective 5-HT reuptake inhibitor (SSRI) escitalopram did not modify
GVRs, whereas the SSRI paroxetine dose-dependently inhibited GVRs in
female rabbits (43.3 and 53.1% at 5 mg/kg). GVRs were also significantly
inhibited by the 5-HT and NE reuptake inhibitors venlafaxine (53.4 and
52.6% at 5 mg/kg) and duloxetine (40.9 and 37.4% at 1 mg/kg). l-arginine
prevented the inhibitory effects of paroxetine (105.5 and 115.3%) and
partially prevented duloxetine-induced reduction of GVRs but had no
effect on the inhibition of GVRs induced by venlafaxine. Conversely, the
alpha-adrenergic receptor blocker phentolamine had no effect on
paroxetine-induced reduction of GVRs, partially prevented the inhibitory
effects of duloxetine, and fully prevented the effects of venlafaxine
(93.0 and 96.7%). Duloxetine-induced inhibition of GVRs was completely
prevented by combined administration of l-arginine and phentolamine
(123.5 and 103.6%). Although 5-HT or the highly selective SRI
escitalopram did not inhibit GVRs, NE or inhibition of nitric oxide (NO)
synthesis did. Inhibition of the NO pathway by paroxetine and duloxetine
or activation of alpha-adrenergic mechanisms by venlafaxine and
duloxetine lead to antidepressant-induced inhibition of GVRs in female
rabbits.PMID: 15034084
poster:Dave001
thread:367831
URL: http://www.dr-bob.org/babble/20040719/msgs/368087.html