Mechanism of Apomorphine in Male Sexual Function
Apomorphine acts as a centrally-acting dopamine D1/D2 receptor agonist that triggers penile erection primarily through activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus, with additional effects on pro-erectile sacral parasympathetic pathways in the spinal cord. 1, 2
Central Dopaminergic Mechanism
The mechanism involves multiple levels of the central nervous system:
Hypothalamic activation: Apomorphine stimulates dopamine receptors in the paraventricular nucleus (PVN), which triggers oxytocin release. This oxytocinergic pathway descends from the hypothalamus to brainstem and spinal autonomic centers that control erectile function 3
Cortical effects: Brain imaging studies demonstrate that apomorphine increases cerebral activity in the right superior prefrontal cortex (Brodmann area 6) and anterior cingulate cortex during sexual stimulation, areas associated with sexual arousal and erectile response 4
Oxytocin elevation: Clinical evidence shows oxytocin plasma levels increase in both systemic and cavernous blood during the transition from flaccidity to tumescence and rigidity, supporting oxytocin's pivotal role in the erectile mechanism triggered by dopaminergic stimulation 3
Mesolimbic involvement: The dopaminergic system affects sexual motivation through the nucleus accumbens (appetitive phase) and the median preoptic area (consummatory phase), though these effects are part of dopamine's broader role in reward and cognitive processes 1
Clinical Context and Limitations
Importantly, apomorphine is inferior to PDE-5 inhibitors for erectile dysfunction. The 2009 American College of Physicians guidelines explicitly state that sildenafil was more effective than sublingual apomorphine in improving erectile function, frequency of penile penetration, erection maintenance, and percentage of successful intercourse attempts 5
Common Pitfall
The FDA-approved formulations of apomorphine (subcutaneous) are indicated for Parkinson's disease, not erectile dysfunction. While priapism has been reported in 3 of 361 men receiving subcutaneous apomorphine injections in clinical studies, this was in the context of Parkinson's treatment 6
Effects in Females
Apomorphine does NOT have established efficacy for female sexual dysfunction and is not recommended for this indication. 7
The 2017 NCCN Survivorship guidelines explicitly state: "Currently, the panel does not recommend the use of oral phosphodiesterase type 5 inhibitors (PDE5i) for female sexual dysfunction due to the lack of data regarding their effectiveness in women. Although thought to increase pelvic blood flow to the clitoris and vagina, PDE5i showed contradictory results in RCTs of various noncancer populations of women being treated for sexual arousal disorder. More research is needed before a recommendation can be made regarding the use of sildenafil for the treatment of female sexual dysfunction." 7
Key Distinction
While the mechanism describes how dopamine affects male erectile pathways through oxytocin and hypothalamic-spinal circuits, the counterpart of such regulation of genital arousal by dopamine has not been established in females 1. The anatomical and neurochemical pathways that make apomorphine effective in males simply have not been demonstrated to produce comparable effects in female sexual function.