5-HT_1Areceptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats: https://academic.oup.com/ijnp/article/12/8/1045/677907?login=false

• “The present study was conducted to evaluate the ability of acute or chronic treatment with 5-HT_1A antagonists to alter chronic fluoxetine-induced impairments in sexual function. Chronic 14-d treatment with fluoxetine resulted in a marked reduction in the number of non-contact penile erections in sexually experienced male rats, relative to vehicle-treated controls.
• Acute administration of the 5-HT_1A antagonist WAY-101405 resulted in a complete reversal of chronic fluoxetine-induced deficits on non-contact penile erections at doses that did not significantly alter baselines.
• Chronic co-administration of the 5-HT_1A antagonists WAY-100635 or WAY-101405 with fluoxetine prevented fluoxetine-induced deficits in non-contact penile erections in sexually experienced male rats.
• Moreover, withdrawal of WAY-100635 from co-treatment with chonic fluoxetine, resulted in a time-dependent reinstatement of chronic fluoxetine-induced deficits in non-contact penile erections. Additionally, chronic administration of SSA-426, a molecule with dual activity as both a SSRI and 5-HT_1A antagonist, did not produce deficits in non-contact penile erections at doses demonstrated to have antidepressant-like activity in the olfactory bulbectomy model. Taken together, these data suggest that 5-HT_1A antagonist treatment may have utility for the management of SSRI-induced sexual dysfunction.”

What are the widely available 5HT1A antagonists? 

@desperate_science 

There aren’t too many 5-HT1A antagonists that are available over the counter – or at least there aren’t too many supplements that are conclusively proven to act as 5-HT1A antagonists.

However one such supplement that does have some clinical evidence for modulating 5-HT1A is Yohimbine/Rauwolscine. These are alkaloids isolated from certain plants such as Rauvolfia, that have a long history of use as aphrodisiacs. 

Whilst their efficacy as aphrodisiacs has been attributed to their action on the alpha2-adrenergic receptor, the 5-HT1A receptor could also be involved in this effect. Whilst not strictly an antagonist, Rauwolscine and Yohimbine are partial agonists of 5-HT1A, which block the stronger agonists (such as 8-0H-DPAT) through competitive inhibition. [1]

The activity ratio of Rauwolscine and Yohimbine were 0.70 and 0.59, respectively, when compared to the full agonist serotonin. However studies investigating the use of Yohimbine for resolving SSRI induced sexual dysfunction failed to find a significant effect. [2] This could be to do with the highly dose dependent effect of Yohimbine given it’s partial agonist activity, with high doses activating 5-HT1A, whilst lower doses lower serotonergic tonus by binding to the autoreceptor. [3]

[1] https://www.sciencedirect.com/science/article/abs/pii/000629529390208E

[2] https://www.sciencedirect.com/science/article/abs/pii/S0022395601000607

[3]  https://www.sciencedirect.com/science/article/abs/pii/S0304394015301348