Common stereospecificity of opioid and dopamine systems for N-butyrophenone prodine-like compounds.
The two optical isomers of 1-[3-(p-fluorobenzoyl) propyl]-3-methyl-4-phenyl-4-propionoxypiperidine (FPP) were obtained by resolution of (+/-)-r-3-methyl-4-phenyl-c-4-piperidinol followed by N-alkylation and O-propionylation. These, as well as the racemate, were evaluated for their antinociceptive, opioid, and neuroleptic properties using in vivo and in vitro test systems. The results are remarkable in two respects, namely, the dextrorotatory isomer is consistently the most potent on all tests, and it acts on both opioid (mu) and neuroleptic (D2) receptors.
Iorio
M A
MA
Pharmaceutical Chemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy.
Frigeni
V
V
Bowman
E R
ER
Harris
L S
LS
May
E L
EL
Aceto
M D
MD
D000522:Alphaprodine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000698:Analgesia; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D001058:Apomorphine / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D007202:Indicators and Reagents; D007536:Isomerism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu; D013134:Spiperone / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship
D000700:Analgesics; D014150:Antipsychotic Agents; D007202:Indicators and Reagents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000522:Alphaprodine; C067174:1-(3-(4-fluorobenzoyl)propyl)-3-methyl-4-phenyl-4-propionoxypiperidine; D013134:Spiperone; D004090:Dihydromorphine; D001058:Apomorphine