Activation of melanocortin MC4 receptors increases erectile activity in rats ex copula

European Journal of Pharmacology

Volumn 454, Issue 1, 2002, Pages 71-79

  Martin, William J ^a   McGowan, Erin ^a   Cashen, Doreen E ^a   Gantert, Liza T ^a   Drisko, Jennifer E ^a   Hom, Gary J ^a   Nargund, Ravi ^a   Sebhat, Iyassu ^a   Howard, Andrew D ^a   Van der Ploeg, Lex H T ^a   MacIntyre, D Euan ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Erectile dysfunction; G protein coupled receptor; Melanocortin; Melanocortin MC4 receptor

Indexed keywords

1 [[[2 [2 AMINO 4 (METHYLSULFONYL)BUTYRAMIDO] 7,7 DIMETHYLBICYCLO[2.2.1]HEPTAN 1 YL]METHYL]SULFONYL] 4 (2 METHYLPHENYL)PIPERAZINE; AGOUTI RELATED PROTEIN; APOMORPHINE; ISOQUINOLINE DERIVATIVE; MELANOCORTIN; MELANOCORTIN 4 RECEPTOR; MPB 10; N (1,2,3,4 TETRAHYDROISOQUINOLINIUM 3 YLCARBONYL) 1 (4 CHLOROBENZYL) 2 [4 CYCLOHEXYL 4 (1H 1,2,4 TRIAZOL 1 YLMETHYL)PIPERIDIN 1 YL] 2 OXOETHYLAMINE; OXYTOCIN ANTAGONIST; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; AGOUTI RELATED PROTEIN (83 132); AGOUTI-RELATED PROTEIN-(83-132); BORNANE DERIVATIVE; CORTICOTROPIN RECEPTOR; CYCLOPEPTIDE; MBP10 PEPTIDE; N (1,2,3,4 TETRAHYDROISOQUINOLINIUM 3 YLCARBONYL) 1 (4 CHLOROBENZYL) 2 (4 CYCLOHEXYL 4 (1H 1,2,4 TRIAZOL 1 YLMETHYL)PIPERIDIN 1 YL) 2 OXOETHYLAMINE; N-(1,2,3,4-TETRAHYDROISOQUINOLINIUM-3-YLCARBONYL)-1-(4-CHLOROBENZYL)-2-(4-CYCLOHEXYL-4-(1H-1,2,4-TRIAZOL-1-YLMETHYL)PIPERIDIN-1-YL)-2-OXOETHYLAMINE; PEPTIDE FRAGMENT; PIPERAZINE DERIVATIVE; TETRAHYDROISOQUINOLINE DERIVATIVE; TRIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG SELECTIVITY; GROOMING; LATENT PERIOD; MALE; MECHANICAL STIMULATION; NONHUMAN; PENIS ERECTION; PRIORITY JOURNAL; RAT; REFLEX; REPRODUCIBILITY; STRETCHING; TELEMETRY; YAWNING; ANIMAL; BINDING COMPETITION; COMPARATIVE STUDY; DRUG ANTAGONISM; DRUG POTENTIATION; PHYSIOLOGY; SPRAGUE DAWLEY RAT;

ANIMALS; BINDING, COMPETITIVE; BORNANES; DOSE-RESPONSE RELATIONSHIP, DRUG; ISOQUINOLINES; MALE; PENILE ERECTION; PEPTIDE FRAGMENTS; PEPTIDES, CYCLIC; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, MELANOCORTIN, TYPE 4; RECEPTORS, CORTICOTROPIN; TETRAHYDROISOQUINOLINES; TRIAZOLES;

EID: 0036842081     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0014-2999(02)02479-2     Document Type: Article

References (29)

1. Adan R.A., Gispen W.H. Melanocortins and the brain: from effects via receptors to drug targets. Eur. J. Pharmacol. 405:2000;13-24.
2. Adan R.A., Szklarczyk A.W., Oosterom J., Brakkee J.H., Nijenhuis W.A., Schaaper W.M., Meloen R.H., Gispen W.H. Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat. Eur. J. Pharmacol. 378:1999;249-258.
3. Andersson K.E. Pharmacology of penile erection. Pharmacol. Rev. 53:2001;417-450.
4. Andersson K.E., Wagner G. Physiology of penile erection. Physiol. Rev. 75:1995;191-236.
5. Andersson K.E., Gemalmaz H., Waldeck K., Chapman T.N., Tuttle J.B., Steers W.D. The effect of sildenafil on apomorphine-evoked increases in intracavernous pressure in the awake rat. J. Urol. 161:1999;1707-1712.
6. Argiolas A. Neuropeptides and sexual behaviour. Neurosci. Biobehav. Rev. 23:1999;1127-1142.
7. Argiolas A., Melis M.R., Vargiu L., Gessa G.L. D(CH2)5Tyr(Me)-[Orn8]vasotocin, a potent oxytocin antagonist, antagonizes penile erection and yawning induced by oxytocin and apomorphine, but not by ACTH-(1-24). Eur. J. Pharmacol. 134:1987;221-224.
8. Argiolas A., Melis M.R., Murgia S., Schioth H.B. ACTH- and alpha-MSH-induced grooming, stretching, yawning and penile erection in male rats: site of action in the brain and role of melanocortin receptors. Brain Res. Bull. 51:2000;425-431.
9. Bednarek M.A., MacNeil T., Kalyani R.N., Tang R., Van der Ploeg L.H., Weinberg D.H. Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. J. Med. Chem. 44:2001;3665-3672.
10. Bernabe J., Rampin O., Giuliano F., Benoit G. Intracavernous pressure changes during reflexive penile erections in the rat. Physiol. Behav. 57:1995;837-841.
11. Bernabe J., Rampin O., Sachs B.D., Giuliano F. Intracavernous pressure during erection in rats: an integrative approach based on telemetric recording. Am. J. Physiol. 276:1999;R441-R449.
12. Bertolini A., Gessa G.L. Behavioral effects of ACTH and MSH peptides. J. Endocrinol. Investig. 4:1981;241-251.
13. Bertolini A., Vergoni W., Gessa G.L., Ferrari W. Induction of sexual excitement by the action of adrenocorticotrophic hormone in brain. Nature. 221:1969;667-669.
14. Gessa G.L., Pisano M., Vargiu L., Crabai F., Ferrari W. Stretching and yawning movements after intracerebral injection of ACTH. Rev. Can. Biol. 26:1967;229-236.
15. McKenna K.E. Some proposals regarding the organization of the central nervous system control of penile erection. Neurosci. Biobehav. Rev. 24:2000;535-540.
16. Mizusawa H., Hedlund P., Andersson K.E. Alpha-melanocyte stimulating hormone and oxytocin induced penile erections, and intracavernous pressure increases in the rat. J. Urol. 167:2002;757-760.
17. Mountjoy K.G., Mortrud M.T., Low M.J., Simerly R.B., Cone R.D. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8:1994;1298-1308.
18. Roselli-Rehfuss L., Mountjoy K.G., Robbins L.S., Mortrud M.T., Low M.J., Tatro J.B., Entwistle M.L., Simerly R.B., Cone R.D. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U. S. A. 90:1993;8856-8860.
19. Sachs B.D. Contextual approaches to the physiology and classification of erectile function, erectile dysfunction, and sexual arousal. Neurosci. Biobehav. Rev. 24:2000;541-560.
20. Schioth H.B., Mutulis F., Muceniece R., Prusis P., Wikberg J.E. Discovery of novel melanocortin 4 receptor selective MSH analogues. Br. J. Pharmacol. 124:1998;75-82.
21. Sebhat I.K., Martin W.J., Ye Z., Barakat K., Mosley R.T., Bakshi R., Palucki B., Constantin Tamvakopoulos C., Weinberg D.H., MacNeil T., Kalyani R.N., Tang R., Stearns R.A., Mille R.R., Strack A.M., McGowan E., Cashen D.E., Drisko J.E., Hom G.J., Howard A.D., MacIntyre D.E., Van der Ploeg L.H.T., Patchett A.A., Nargund R.P. Design and Pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium-3-ylcarbonyl]-(1R)-1-(4- chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine, a potent, selective, melanocortin subtype-4 receptor (MC4R) agonist. J. Med. Chem. 42(21):2002;4589-4593.
22. Van der Ploeg L.H.T., Martin W.J., Howard A.D., Nargund R.P., Austin C.P., Guan X., Drisko J., Cashen D., Sebhat I., Patchett A.A., Figueroa D.J., Dilella A.G., Connolly B.M., Weinberg D.H., Tan C.P., Palyha O.C., Pong S.-S., MacNeil T., Rosenblum C., Vongs A., Tang R., Yu H., Sailer A., Fong T.M., Huang C., Tota M.R., Chang R.S., Stearns R., Tamvakopoulos C., Christ G., Drazen D.L., Spar B.D., Nelson R.J., MacIntyre D.E. A role for the melanocortin 4 receptor in sexual function. Proc. Natl. Acad. Sci. U. S. A. 99:2002;11381-11386.
23. Vemulapalli R., Kurowski S., Salisbury B., Parker E., Davis H. Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO. Br. J. Pharmacol. 134:2001;1705-1710.
24. Vergoni A.V., Bertolini A., Mutulis F., Wikberg J.E., Schioth H.B. Differential influence of a selective melanocortin MC4 receptor antagonist (HS014) on melanocortin-induced behavioral effects in rats. Eur. J. Pharmacol. 362:1998;95-101.
25. Vergoni A.V., Bertolini A., Guidetti G., Karefilakis V., Filaferro M., Wikberg J.E., Schioth H.B. Chronic melanocortin 4 receptor blockage causes obesity without influencing sexual behavior in male rats. J. Endocrinol. 166:2000;419-426.
26. Wessells H., Fuciarelli K., Hansen J., Hadley M.E., Hruby V.J., Dorr R., Levine N. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J. Urol. 160:1998;389-393.
27. Wessells H., Gralnek D., Dorr R., Hruby V.J., Hadley M.E., Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 56:2000;641-646.
28. Wikberg J.E., Muceniece R., Mandrika I., Prusis P., Lindblom J., Post C., Skottner A. New aspects on the melanocortins and their receptors. Pharmacol. Res. 42:2000;393-420.
29. Williams P.D., Anderson P.S., Ball R.G., Bock M.G., Carroll L., Chiu S.H., Clineschmidt B.V., Culberson J.C., Erb J.M., Evans B.E.et al. 1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo [2.2.1]-heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperazine (L-368,899): an orally bioavailable, non-peptide oxytocin antagonist with potential utility for managing preterm labor. J. Med. Chem. 37:1994;565-571.