- Sexualite
- Published:
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
Andrologie volume 1, pages 83–84 (1991)
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
References
-Aboseif S.R., Breza J., Diederichs W., Bosch R., Benard F. Stief C.G., Lue T.F., Tanagho E.A.: Effect of chronic intracavernous injection of papaverine and prostaglandin E 1 on erectile tissue in monkeys. J. Urol., 1988, 139: 257–259.
-de Groat W.C., Steers W.D.: Neuroanatomy and neurophysiology of penile erection. In Contemporary management of impotence and infertility, ed by Tanagho, E.A. Williams and Wilkins. Baltimore, 1988
-de Tejada S.I., Blanco R., Goldstein I, Azadzoi K., Morenas A. Krane R, Cohen R.A. Cholinergic neurotransmission in human corpus cavernosum. Am. J. Physiol. 1989, 254: 459–462.
-de Tejada I.S., Goldstein I., Azadzoi K., Krane R., Cohen R. Impaired new neurogenic and endothelium mediated relaxation of penile smooth muscle from diabetic men with impotence. New Engl. J. Med., 1989, 320: 1025–1027
-Furchgott R.F.: Studies on endothelium dependant vasodilatation and the endothelium derived relaxing factor. Acta Physiol. Scand., 1990, 139: 257–265
-Furchtgott R.F., Zawadski J.V.: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature (Lond.), 1980: 288: 373–375
-Holmquist F., Hedlund H., Andersson K.E. Characterisation of inhibitory neurotransmission in the isolated corpus cavernosum from rabbit and man. In: Holquist F. Nonadrenergic, noncholinergic mechanisms for contraction and relaxation of penile smooth muscle. Lund University Thesis 1991, pp 109–130
-Holmquist F., Hellund H, Andersson K.E., L N-nitro arginine inhibits non-adrenergic, non cholinergic relaxation of human isolated corpus cavernosum. Acta Physiol. Scand., 1991, 141: 441–442
-Holmquist F., Stief C.G., Jonas U., Andersson K.E. Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit. Acta Physiol. Scand. sous presse.
-Ignarro J.L. Biosynthesis and metabolism of endothelium-derived relaxing nitric oxide. Ann. Rev. Pharmacol. Toxicol. 1990, 30: 535–537
-Jünemann K.P., Alken P., Pharmacotherapy of erectile dysfunction. Int. J. Impotence Res. 1989, 1: 71–94.
-Kim N., Azadzoi K.M., Goldstein I., de Tejada S.I.. A nitric oxide-like factor mediates non-adrenergic non-cholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J. Clin. Invest. 1991, 88: 112–113
-Lue T.F., Takamura T, Schmidt R.A., Tanagho E.A.: Hemodynamics of erection in the monkey. J. Urol. 1983, 130: 1237–1241
-Reden J.: Molsidomine, Blood Vessels. 1990, 27: 282–294
-Stief C.G., Djamilian M., Schaebsdau F., Truss M., Schlick R., Abicht J., Allhoff E.P., Jonas U. Single potential analysis of cavernous electric activity. World J. Urol., 1990, 8: 75–79
-Stief C.G., Bähren W., Gall H, Scherb W. Functional evaluation of penile hemodynamics. J. Urol. 1988, 139: 734–737
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stief, C.G., Holmquist, F. & Andersson, K.E. Resultats preliminaires d’injections intracaverneuses d’un donneur d’oxyde d’azote (NO), la linsidomine, dans le traitement de l’impuissance. Androl. 1, 83–84 (1991). https://doi.org/10.1007/BF03034179
Issue Date:
DOI: https://doi.org/10.1007/BF03034179