Narcotics and rat testicular metabolism
Jakubovic, A.; McGeer, E.G.
Molecular Pharmacology 16(3): 970-980
1979
ISSN/ISBN: 0026-895X PMID: 530266 Document Number: 148470
Methadone (Me), the synthetic narcotic analgesic, is widely used in maintenance programs for the chronic treatment of morphine (Mo) and heroin (He) dependent persons. The effect of various narcotic analgesics on protein and nucleic acid synthesis in rat testicular cell suspensions and on testosterone (T) production in rat testis was studied. Racemic methadone (dl-Me), 1- and d-Me, 1-.alpha.-acetyl-methadol (LAM) and dl-Me metabolites, 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) and 2-ethyl-1,5-dimethyl-3,3-diphenyl-pyrrolinium (EDDP), at 100 and 10 .mu.M had a dose-related, significant effect on L-AMP. In comparable experiments, He or Mo were far less inhibitory. T production by dibutyryl-cAMP stimulated testicular Leydig cell preparations was reduced by dl-Me and the ID50 was about 9 .mu.M. Some narcotic analgesics such as dl-Me, LAM and their metabolites may reduce testicular T synthesis by virtue of their direct inhibitory effects on RNA and/or protein synthesis. He and Mo may decrease T levels primarily through the hypothalamic-pituitary-gonadal axis. A combination of central and peripheral action of some narcotics cannot be excluded.