The evaluation of apomorphine for the treatment of erectile dysfunction

Abstract

Apomorphine SL is more effective than placebos in treating ED and is generally well tolerated in the sublingual formulation, causing tolerable side effects. Newer nasal-spray formulations provide faster efficacy. Its efficacy in patients with multiple co-morbidities is more limited. However, it is not as effective as PDE5-I in the treatment of ED. Its most significant strength is its safety profile. It may have a niche in the treatment ED in patients who have failed treatment with, or are intolerant to other well-established pharmacological treatment for ED (e.g., PDE5-Is). Apomorphine is not a first-line treatment option for patients with ED, especially as it is no more widely available in the western world.

New tricks for an old dog: A repurposing approach of apomorphine

“…This complex and multifactorial disorder (Costa, 2003) is defined as a "persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual intercourse" (NIH Consensus Conference, 1993). As penile erection is regulated both centrally (dopamine and melanocortin-receptors) and peripherally (nitric oxide -NO-and stimulation of smooth muscle relaxation), numerous factors can contribute to ED: endothelial dysfunction (vascular disorders), systemic, psychological and/or neurological disorders, hormonal factors, advancing age and/or iatrogenic causes (MacLennan et al, 2004;Afif-Abdo et al, 2008;Albersen et al, 2010;Mohee et al, 2012).…”

“…Erection usually occurred within 20 min (Altwein & Keuler, 2001) with an overall good tolerability. Adverse events were usually mild to moderate: headache, nausea/vomiting, dizziness, yawning, hypotension/vasovagal-type symptoms, chest pain, mouth ulceration, taste perversion or stomatitis (the latter being due to the sublingual administration) (Altwein & Keuler, 2001;Giuliano & Allard, 2002;Montorsi, 2003b;Perimenis et al, 2004;Mohee et al, 2012). Hypersensitivity reactions (facial edema) or syncope occurred very rarely (MacLennan et al, 2004;Afif-Abdo et al, 2008;Altwein & Keuler, 2001).…”

“…When considering a customized approach (Heaton, 2001), apomorphine remains relevant in ED, particularly for a subset of patients (Mohee et al, 2012), where it can even represent a first-line oral therapy (Heaton, 2001;Montorsi, 2003b;Perimenis et al, 2004;Albersen et al, 2010). A new inhalation device administering lower doses of apomorphine (VR004) was developed at the end of the 2000's and seemed rather promising (Riley et al, 2010), but its development for male sexual dysfunction has been suspended, apparently due to lack of partners (Albersen et al, 2010).…”

Consenso de la Asociación Colombiana de Neurología sobre el uso de apomorfina en la enfermedad de Parkinson

“…En 1891, Gee descubrió que la apomorfina podría desencadenar estereotipias en perros, roedores y otros animales que son incapaces de vomitar y a finales del siglo XIX la apomorfina se convirtió en un fármaco útil para una variedad de trastornos psiquiátricos como el delirium tremens (en la adicción al alcohol), esquizofrenia, manía, depresión e insomnio. Durante las pruebas en la dependencia al alcohol se hizo otra observación interesante: se informaron erecciones espontáneas en 30 % a 55 % de los individuos, lo que más de 100 años después, condujo a una introducción temporal en el mercado de Uprima® como una terapia para la disfunción eréctil (8,9). Harnack realizó en 1874 los primeros experimentos farmacológicos detallados de apomorfina en mamíferos y ranas y llegaron a la conclusión que la apomorfina actúa en diferentes centros cerebrales involucrando el comportamiento, así como el control respiratorio y cardiovascular (1).…”

“…El uso generalizado de la apomorfina en la enfermedad de Parkinson se vio obstaculizado por su pobre biodisponibilidad y perfil inicial de efectos secundarios que podían llegar a ser muy incapacitantes reflejando la actividad agonista dopa (2,7,8,13). Para las náuseas, Corsini, et al, en 1979, mostraron que la domperidona, un antagonista de la dopamina periférica que no penetra la barrera hematoencefálica, bloquea los efectos adversos no deseados de la apomorfina, facilitando la investigación adicional con apomorfina (14).…”