AM630 antagonism of cannabinoid-stimulated [35S]GTP gamma S binding in the mouse brain.
This research was designed to determine the action of the novel aminoalkylindole AM630 (6-iodo-pravadoline) at the cannabinoid receptor by studying its interaction with the cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-y]-(1-naphthalenyl)methanone mesylate) on guanosine-5'-O-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding in mouse brain. WIN 55,212-2 stimulated [35S]GTP gamma S binding, while AM630 had no effect. AM630 antagonized WIN 55,212-2-2induced [35S]GTP gamma S binding and shifted the WIN 55,212-dose-response curve to the right. These results clearly demonstrate that AM630 exerts cannabinoid receptor antagonist properties in the brain.
Hosohata
Y
Y
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724, USA.
Quock
R M
RM
Hosohata
K
K
Makriyannis
A
A
Consroe
P
P
Roeske
W R
WR
Yamamura
H I
HI
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002186:Cannabinoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors
D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094023:iodopravadoline