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INTRACAVERNOSAL AGENTS

Vasoactive intestinal polypeptide and phentolamine
Vasoactive intestinal polypeptide (VIP) is a postganglionic neurotransmitter which seems to have a role in the erectile process. VIP is described as a ‘facilitator’ of erections because intracavernosal injection leads to tumescence only. A combination of VIP and phentolamine can be very effective. In a study of 52 men with erectile dysfunction of mixed aetiology but full response to papaverine, intracorporeal injection of 30 ug of VIP and 0.5-2 mg of phentolamine led to a functionally rigiderection in 100% of cases. At 6 months follow-up no patient had complained of pain or suffered a complication such as corporeal fibrosis or priapism. VIP and phentolamine would seem to be a very promising, safe and efficacious treatment for erectile dysfunction and maybe an especially important alternative for patients who suffer PGEl-induced pain. At present this combina tion is currently only available on a named-patient basis in hospitals.

Moxisylyte hydrochloride
Moxisylyte is an a 1-blocker and has erectogenic activity by antagonising noradrenaline. In a placebo-controlled study of men with neurogenic erectile dysfunction an injection of 10-30 mg of moxisylyte resulted in a full erection in 58% compared with none in the placebo group. More recently, in a comparative study, intracavernosal injection of moxisylyte resulted in successful sexual intercourse in 46% of patients compared with 81% of patients using PGEl. PGEl is a more effective treatment for erectile dysfunction than moxisylyte but moxisylyte may have a role in patients with PGEl-induced pain, fibrosis, or priapism. Online Pharmacy

Linsidomine (SIN-1)
SIN-1 is the active metabolite of the anti-anginal drug molsinomine. It liberates nitric oxide (NO) and this leads to cavernosal smooth muscle relaxation through the cGMP pathway. Initial studies with SIN-1 appeared promising with 46% of men with erectile dysfunction of mixed aetiology attaining a functional erection, while in a group of patients with psychogenic and neurogenic erectile dysfunction, 97.8% of patients were satisfied by their response to SIN-1. More recently, however, in a double-blind comparative cross-over study with SIN-1 and PGEl, SIN-1 did not produce a functional erection in any of the 40 patients. The authors concluded that PGEl was superior and that “there can be no place for SIN-1 in the treatment of erectile dysfunction“.

Nitroprusside
Nitroprusside also leads to cavernosal smooth muscle relaxation through cyclic GMP (cGMP) by its ability to release NO. In a single-blind cross-over study in 60 patients comparing 300 ug of nitroprusside with 20 ug of PGEl, 15% of patients attained a full erection with nitroprusside compared with 20% with PGEl. However, nitroprusside is chemically unstable and can cause significant hypotension. For these reasons, its role in the treatment of erectile dysfunction would seem limited.

Calcitonin-gene-related-peptide
Calcitonin-gene-related-peptide is thought to be a parasympathetic neurotransmitter and has been shown in vitro to relax strips of cavernosal smooth muscle. By itself it has been shown to cause tumescence but not rigidity. In combination with PGEl, 56% of patients had a full erection, however, as there was no comparison with PGEl alone in the study, the role of calcitonin-gene-related-peptide is not clear. Also, to date, follow-up is too short to say whether its use leads to reduced pain, fibrosis, or priapism rate.

Chlorpromazine
In a 2-year study with 163 patients, a mixture of PGEl and chlorpromazine was shown to be as effective as PGEl and phentolamine. Chlorpromazine may therefore be a useful substitute for phentolamine, as it is less expensive. It has also been shown that when chlorpromazine is substituted for phentolamine in combinations with papaverine or papaverine-plus-PGEl there is no loss of efficacy. CanadianPharmacy mall