Pharmacological evaluation of 2-amino-6(7)- and 9-amino-6-trifluoromethylbenzonorbornenes, the conformationally rigid analogues of norfenfluramine in mice.
1. The possible role of conformational requirements which fenfluramine and norfenfluramine must satisfy to elicit its observed pharmacological activities was investigated in mice with the use of four conformationally-rigid norfenfluramine analogues. 2. In this study, both the syn-9-amino and endo-2-amino isomers, which structurally resemble the gauche conformation of norfenfluramine, were found to have little or no effect on spontaneous locomotor activity. 3. On the other hand, the isomers (i.e. the anti-9-amino and exo-2-amino isomers) that mimic the anti conformation of norfenfluramine were capable of causing a decrease in spontaneous motor activity similar to that of norfenfluramine. 4. The analgesic activities of these rigid analogues were also assessed and all of the isomers were found to be weakly analgesic. 5. Only the exo-2-amino isomer exhibited analgesic potency similar to that of fenfluramine. Furthermore all of these compounds were capable of enhancing the analgesic activity of morphine.
Gray
N M
NM
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612.
Lu
M C
MC
Bhargava
H N
HN
D000661:Amphetamine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D008968:Molecular Conformation; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009636:Norbornanes / Q000737:chemistry / Q000494:pharmacology*; D009642:Norfenfluramine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects
D000700:Analgesics; D009636:Norbornanes; D009642:Norfenfluramine; D005277:Fenfluramine; D009020:Morphine; C041088:9-amino-6-trifluoromethylbenzonorbornene; D000661:Amphetamine