(+)-6,7-benzomorphan sigma ligands stimulate dopamine synthesis in rat corpus striatum tissue.
The benzomorphan sigma ligands, (+)-N-allylnormetazocine (NANM) and (+)-pentazocine, but not (+)-cyclazocine, stereospecifically stimulated dopamine synthesis in minces of rat corpus striatum by 15-23% over basal values at 0.1-1.0 microM. The effect of (+)-NANM and (+)-pentazocine was blocked by the reported sigma antagonist, BMY-14802 but not by the opiate antagonist naloxone. These results suggest that these (+)-benzomorphans may act as agonists at putative sigma heteroreceptors on striatal nerve terminals, or through an indirect mechanism, to modulate dopamine synthesis.
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
R G
RG
Booth
R J
RJ
Baldessarini
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003496:Cyclazocine / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D013237:Stereoisomerism; D013268:Stimulation, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001575:Benzomorphans; D002395:Catecholamines; D008024:Ligands; D011957:Receptors, Opioid; D017480:Receptors, sigma; C012134:SK&F 10047; D014446:Tyrosine 3-Monooxygenase; D010620:Phenazocine; D003496:Cyclazocine; D010423:Pentazocine; D004298:Dopamine