Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug.
An exclusive central site of action for the proerectile effect of apomorphine, including not only the brain but also the spinal cord, is supported by extensive experimental data. Assuming that the mechanisms of action of apomorphine are similar in humans and animal models, its use for the treatment of erectile dysfunction (ED) validates the emerging idea that erectile response could be enhanced by acting directly within the central nervous system (CNS). It also emphasized the key role of the dopaminergic system in the control of erection. As exemplified with the clinical development of apomorphine, targeting the CNS does not rule out the occurrence of undesirable side effects. Because the rare event of syncope induced by apomorphine is not well understood, further research should be conducted to explore its possible mechanisms. In clinical practice, however, approved doses of apomorphine SL are well tolerated. It is noteworthy that no modification of sexual desire was observed with apomorphine. Indeed, drugs acting within the CNS may more likely interact with sexual desire than peripherally acting drugs, and care should be taken to assess this point in the future. Although our knowledge of the control of penile erection by the CNS is restricted, there are many potential sites for CNS-acting ED drugs. New centrally acting therapy for ED should concentrate on receptor targets more specific to erectile command. Clinical efficacy of new centrally-acting compounds will assess the well-founded purpose of this rationalization.
Giuliano
F
F
Department of Urology, CHU de Bicêtre, Assistance Publique Hôpitaux de Paris, France. giuliano@cyber-sante.org
Allard
J
J
D000818:Animals; D001058:Apomorphine / Q000009:adverse effects*; D015259:Dopamine Agents / Q000009:adverse effects*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010410:Penile Erection / Q000187:drug effects
D015259:Dopamine Agents; D001058:Apomorphine