Mode of action: Apomorphine is a centrally acting drug for the treatment of ED; it is not approved in the United States, although it is available in Europe. CNS control of sexual function is thought to be maintained through a balance of inhibitory and excitatory systems, influenced by androgens and by erectogenic stimuli from centers of the brain concerned with sight, sound, smell, touch, and cognition. A variety of neurotransmitters are involved but, simplistically, the primary neurotransmitter of central sexual inhibition is serotonin, and of central sexual excitation, dopamine. Apomorphine activates dopamine D2 receptors in the hypothalamus and has the potential to both initiate an erection and enhance responsiveness to erectogenic stimuli.
Use in practice: Proper counseling about the use of any therapy is vital to a successful outcome, but particularly so with ED therapy. Apomorphine is taken sublingually and it is essential that the patient be told to pop it under the tongue, and to allow it to dissolve slowly rather than suck or swallow it. If it is swallowed, it will probably be ineffective, because of the very high proportion of drug metabolized on the first pass through the liver. The 2’mg tablet is pentagonal, and the 3’mg, triangular.
The response rate to apomorphine is significantly less than for the PDE5 inhibitors. A randomized, placebo’controlled, crossover study comparing apomorphine 3 mg with sildenafil 50 mg in the treatment of ED of mixed etiology and severity reported attempts resulting in erections firm enough for intercourse in 44% of men taking apomorphine and 85% of men taking sildenafil [51]. One of the proposed advantages of apomorphine is its relatively rapid onset of action. Clinical trial evidence shows that 71% of responders will achieve an erection within 20 minutes of putting the tablet in their mouths. Apomorphine can be taken once every 8 hours. All men should start with one dose of the 2’mg presentation. They should increase this to 3 mg if the starting dose is well tolerated. Only 15% of men will respond to 2 mg, but dose titration will reduce the risk of users suddenly experiencing unwanted side effects. It is important not to label men ‘nonresponders’ because they do not respond to the first few doses of apomorphine. Some men will give up after just one or two unsuccessful attempts with oral therapy. It should be explained that there is often considerable general and performance anxiety surrounding the use of a new ED medication, which will tend to inhibit erectile responsiveness.
In addition, if men are paying for apomorphine themselves, they may not understand why it is necessary to keep taking a drug that doesn’t work first time. They should be advised to take at least eight doses of 3 mg, in an appropriate environment and with adequate sexual stimulation, before deciding whether or not it is effective for them.
As with PDE5 inhibitors, nonresponders should be closely questioned about how they took the drug, how many doses they had taken, and under what circumstances. Genuine non responders should be offered appropriate alternative therapies. Adverse effects: Because of its relative selectivity for the dopamine D2 receptor, apomorphine is reasonably well’tolerated and there is a low incidence of dopaminergic side effects, such as nausea, vomiting (probably D3 receptors), and hypotension (probably D5 receptors).
In trials of 2’mg and S-mg tablets, 6.8% of men reported nausea, 6.7% reported headaches, 4.4% reported dizziness and 0.2% reported syncope. The reported nausea was usually mild and tended to disappear with repeated use. More than 90% of those men who reported syncope experienced premonitory vasovagal symptoms. Men should be warned not to drive for 2 hours after taking apomorphine, although this is unlikely to be a significant disadvantage for the majority of users. It is sensible to advise users to avoid all potentially dangerous activities, such as climbing ladders or operating machinery, for the same period.
Use in cardiovascular disease: All ED therapies, including apomorphine, are contraindicated in men with severe unstable angina, recent MI (within 4 weeks), severe heart failure or hypotension, and other conditions where sexual activity is inadvisable.
It should be used with caution in men with a history of uncontrolled hypertension, known hypotension, postural hypotension, or those with compromised renal or hepatic function. Apomorphine can be used with caution in men taking anti’hypertensives or nitric oxide donor medications, such as nitrates and nicorandil.
There are published authoritative guidelines on the use of ED therapy in men with cardiovascular disease. Drug interactions: Special care must be taken in prescribing apomorphine to men taking other drugs that act on dopamine receptors, such as antipsychotics and antiemetics, Apomorphine is a dopamine D2 receptor agonist and most antipsychotics are dopamine D2 receptor antagonists. It seems sensible that if a combination is prescribed, then the patient should be foUowed up more carefully for the first weeks of treatment. There is no evidence that the sublingual presentation of apomorphine has any effect on antipsychotic therapy but there may be theoretical risk of precipitating a relapse of psychotic illness. It should not be used in combination with sildenafil or other ED therapies.

Tags: Androgens, Apomorphine, Clinical Trial, Crossover Study, D2 Receptors, Etiology, Excitation, Hypothalamus, Mg Tablet, Neurotransmitter, Neurotransmitters, Pde5 Inhibitors, Randomized, Rapid Onset, Response Rate, Responsiveness, Sexual Function, Sexual Inhibition, Stimuli, Trial Evidence

This entry was posted on Wednesday, March 18th, 2009 at 12:18 am and is filed under Erectile Dysfunction, Orgasm, sexual. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.