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Resultats preliminaires d’injections intracaverneuses d’un donneur d’oxyde d’azote (NO), la linsidomine, dans le traitement de l’impuissance

Preliminary results with the nitric oxyde (NO) donor sin 1 in the treatment of human erectile dysfunction

Abstract

Recent experimental studies showed an important role of endothelium derived relaxing factor (EDRF) for cavernous smooth muscle relaxation. Since nitric oxide (NO) seems to account for the biological actions of EDRF, a study was done to examine a possible role of the NO-donor SIN-1 in the treatment of erectile dysfunction. To determine the therapeutic range, 0.1, 0.2, 0.5 and 1 mg SIN-1 were injected intracavernously in 2 patients with erectile dysfunction each. Then, 40 patients were injected 1 mg SIN-1 including 4 patients that had prolonged erections to minimal doses of papaverine-phentolamine and 4 patients that did not respond with a full erection to other pharmacologic agents. Intracavernous injection of SIN-1 induced a dose dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscle. To 1 mg SIN-1, 19 patients had a full, 14 an almost full and 7 a moderate erection. There were no systemic or local side effects. In the patients with prolonged erections to papaverine-phentolamine, the mean duration of a full erection to SIN-1 was 68 minutes. Compared to a papaverine (15 mg/ml)-phentolamine (0.5 mg/ml) mixture, the erectile response to SIN-1 was superior in 8, comparable in 29 and inferior in 3 patients. Our preliminary data suggest a possible role of SIN-1 for the treatment of erectile dysfunction. The absence of prolonged erections by its spontaneous intracavernous decomposition, a maximal smooth muscle relaxation by a receptor independant action and its low cost indicate its potential to become a standard drug for intracavernous pharmacotherapy.

Resume

Des études récentes faites aussi bien in vitro que in vivo ont montré que le facteur relaxant d’origine endothéliale (EDRF) joue un rôle important dans l’érection. Dans la mesure où l’oxyde d’azote (NO) semble responsable des propriétés biologiques de l’EDRF, nous avons étudié l’effet d’une injection intracaverneuse d’un donneur de NO (Linsodomine ou SIN-1, CORSAVAL intracoronaireR). Pour préciser la dose thérapeutique, nous avons injecté de 0.1 à 1 mg chez 8 patients. Quarante patients, incluant 4 cas présentant des érections prolongées après dose faible de l’association Papavérine-Phentolamine, ont ensuite reçu 1 mg de SIN-1. L’injection a induit une réponse érectile dose-dépendante. Nous n’avons pas observé d’effets secondaires locaux ou systémiques. Chez les cas qui présentaient des érections prolongées avec d’autres drogues vaso-actives la durée moyenne d’érection fut de 68 mn. Nos résultats préliminaires suggèrent l’intérêt du SIN-1 pour le traitement de l’impuissance. Sa demi-vie courte, et sa destruction spontanée dans les corps caverneux, devraient éviter les érections prolongées. Le fait que son action ne soit pas dépendante d’un récepteur, ce qui devrait permettre une relaxation cavemeuse maximale, et son prix modéré font également du SIN-1 une altenative attractive

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Correspondence to Christian G. Stief.

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Key-words

  • erectile dysfunction
  • auto-injection therapy
  • EDRF
  • nitric oxyde Linsidomine

Mots-clés

  • Impuissance
  • auto-injections
  • EDRF
  • oxyde d’azote
  • Linsidomie