More than 90% of cases of erectile dysfunction are organic in nature, the major cause being vascular, although complications of surgical prostatic resection, hormonal disorders, drug use, and neurological disorders all contribute to the etiology of this condition. Transient erectile dysfunction arising for any reason may lead to secondary psychological difficulties that compound the problem. While sildenafil exploded onto the erectile dysfunction market and can be used successfully as a treatment of the underlying organic cause of the condition by many sufferers, treatments of psychogenic erectile dysfunction have advanced more slowly.

As described in our recent overview of male and female sexual dysfunction (click here for access), research surrounding psychogenic erectile dysfunction has centered around three neurotransmitters: serotonin, dopamine and oxytocin. The latter is a neurohypophysial hormone and was, in 1953, the first peptide hormone to have its structure determined and the first to be chemically synthesized. The sequence of the oxytocin receptor was subsequently reported in 1992. The most well known effects of oxytocin include its ability to modulate uterine smooth muscle and lactation. Today, it is accepted that oxytocin exerts a wide spectrum of central and peripheral effects. In the periphery the effects of oxytocin are diverse, including uterine contraction, hemostasis, modulation of kidney electrolyte transport, and control of adipocyte function. Centrally, oxytocin is able to modify sexual function, maternal and feeding behavior, as well as memory and cognition

Oxytocin appears to play a key role in the control of erectile function. Oxytocin binding sites are present in the sacral parasympathetic nucleus and the dorsal grey commissure of the L6-S1 spinal cord, and activation of these receptors is able to cause penile erection. Central, and in particular hippothalmic, hippocampal and/or paraventricular, administration of oxytocin induces erection in the rat. Likewise stimulating oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by GABA and GABA agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. Oxytocin mediates the erectile response to physiological stimuli (ie receptive females) and maintains penile erection in response to penile stimulation, which activates oxytocin-containing neurons in the paraventricular nucleus.

Hence oxytocin receptors play a key role in the central control of penile erection and agonists of this receptor may be of use in the treatment of psychogenic erectile dysfunction. Although a number of oxytocin receptor antagonists have been developed for treating premature labor, few receptor agonists have been developed and this field thus represents an under exploited area of sexual pharmacology.

Entry date February, 2003

Adapted from Melis & Argiolas, Curr Drug Targets 2003 Jan;4(1):55-66 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk