(+)-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.
Booth
R G
RG
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Baldessarini
R J
RJ
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