Moxisylyte: A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in impotence

Abstract

Moxisylyte is a competitive noradrenaline antagonist, acting preferentially on post-synaptic alpha-1 adrenoceptors. It was introduced more than thirty years ago for the treatment of cerebro-vascular disorders and shown more recently effective in the urological field due to its ability to modulate the urethral pressure. Renewal of interest in this drug has been observed in recent years since the demonstration of the possibilities of vasoactive drugs in evaluation and treatment of erectile dysfunctions. Moxisylyte is a prodrug, rapidly transformed into an active metabolite in plasma (Deacetylmoxisylyte or DAM). Elimination of the active metabolite occurs by N-demethylation, sulpho- and glucuroconjugation. The N-demethylated metabolite is sulphoconjugated only. Urine is the main route of excretion. The metabolites of moxisylyte can be determined in biological fluids by various methods using high-performance liquid chromatography. Their pharmacokinetics is dependent on the route of administration. By the oral route, the concentrations of the active metabolite are low, and the glucuroconide of DAM predominates over the sulphates. After intravenous and intracavernous injection, the active metabolite is proportionally higher, the two sulphates are equivalent and in larger amounts than the glucuronide. In the treatment of impotence, intracavernous injection of moxisylyte at 10, 20 or 30 mg can induce an erection adequate for intercourse in most of the patients. Compared to inducing agents such as papaverine and prostaglandin E1, moxisylyte must be considered as a facilitator of male erection, its interest lying in the low rate of adverse effects, either general or local.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Little is known about its pharmacokinetics, but after systemic administration, it has an effect duration of 3 to 4 h. Moxisylyte is a prodrug, rapidly transformed into an active metabolite in plasma (deacetylmoxisylyte). Urine is the main route of excretion (Marquer and Bressolle, 1998).…”

Penile Arteries and Erection

“…Sympathetic preganglionic efferent nerves originate in the intermediolateral nuclei of the thoracolumbar segments (T11-L1) of the spinal cord and synapse in the abdominopelvic paravertebral sympathetic chain, from where the noradrenergic postganglionic nerves join the sacral nerves and reach the penis via the pudendal nerve [27]. Activity in adrenergic nerves causes detumescence of the erect penis [28, 29, 30], and sympathetic tone probably also maintains the penis in the flaccid state, as indicated by the erection induced after injection of α-adrenoceptor antagonists [31, 32]. Moreover, treatment with α 1 -adrenoceptor selective antagonists like prazosin and antidepressive drugs with antiadrenoceptor properties are associated with prolonged erection and priapism [12].…”

Evaluation of oral Ro70-0004/003, an α1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction

“…Indeed, cavernosal a-adrenoceptor blockade is known to produce erection 8 and is used for diagnostic and therapeutic purposes, whilst a-adrenoceptor agonists such as metaraminol may be used to reverse this effect. Furthermore, non selective a-adrenoceptor subtype antagonists such as phentolamine, 19 selective a 1 -adrenoceptor antagonists (eg prazosin and moxisylyte) 20 have been evaluated in clinical trials as possible treatments for MED although the systemic adverse effects of these drugs limits their therapeutic value. Given the known heterogeneity of a 1 -adrenoceptor subtypes, efforts to elucidate the functional a 1 -adrenoceptor subtype in human erectile tissue and develop selective drugs for this target may be therapeutically rewarding.…”