Neurochemical and behavioural effects of hypidone hydrochloride (YL‐0919): a novel combined selective 5‐HT reuptake inhibitor and partial 5‐HT_1A agonist

Abstract

These data suggest that YL-0919 is probably a fast-onset potent antidepressant with few side effects.

Hypidone Hydrochloride (YL-0919) Produces a Fast-Onset Reversal of the Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure

“…Data from another study also demonstrate that YL-0919, together with its significant antidepressant- and anxiolytic-effects, induces a greater impact on extracellular 5-HT levels than the conventional selective 5-HT reuptake inhibitor fluoxetine (Flx). Furthermore, treatment with YL-0919 (7 days vs. Flx 21 days) affected hippocampal synaptic plasticity, thus enhancing long-term potentiation (LTP) in rats, faster than Flx (Zhang et al, 2017 ).…”

YL-0919, a dual 5-HT1A partial agonist and SSRI, produces antidepressant- and anxiolytic-like effects in rats subjected to chronic unpredictable stress

“…When administered via the acute po route, a very low dose of YL-0919 could reduce the immobility time in the tail suspension and forced swimming tests in mice and rats [18] . In a recent study, the GTPγS binding assay was used in determining that YL-0919 is a 5-HT 1A partial agonist [19] . The molecular mechanisms underlying the antidepressant activity of YL-0919 are not clear and need further investigation.…”

Antidepressants and Sexual Dysfunctions: a Translational Perspective

“…In rats, we use the olfactory bulbectomized (OBX) model to detect the onset of antidepressant action of drugs [30]; SSRIs (e.g., paroxetine, escitalopram) only inhibit OBX-induced hyperactivity after chronic, but not acute treatment [29]. In the male rat sexual behavior model, a similar profile emerges; no inhibition of sexual behavior after acute, but after chronic (7-14 days) administration of SSRIs (paroxetine, citalopram, fluoxetine) [16,17,[31][32][33]. Table 1 summarizes the acute and chronic effects of antidepressants and potential antidepressants on sexual behavior in our rat model and also indicates effects in humans (based mainly on effects in either depressed patients or premature ejaculating males).…”

“…Moreover, adding a 5-HT 1Areceptor agonist to an SSRI may counteract SSRI-induced sexual dysfunctions. Hypidone, in preclinical development, has a comparable mechanistic profile like vilazodone and has no sexual inhibitory action either after acute or chronic administration in a comparable sexual behavior model [33]. Another recently developed antidepressant, vortioxetine, is an SSRI with a complex serotonergic profile.…”

“…Various on-demand treatments are in use in males with premature ejaculation, including tramadol, phosphodiesterase type-5 (PDE-5) inhibitors, topical anesthetic Fortacin™ (lidocaine + prilocaine (spray)), and various over-the-counter topical anesthetics (not officially registered) [33]. Tramadol is, based on its μ-opioid agonistic mechanism, mainly used for pain treatment, but has also serotonergic and noradrenergic reuptake inhibiting properties.…”