Ja. Vivian et al., ANALGESIC, RESPIRATORY AND HEART-RATE EFFECTS OF CANNABINOID AND OPIOID AGONISTS IN RHESUS-MONKEYS - ANTAGONIST EFFECTS OF SR 141716A, The Journal of pharmacology and experimental therapeutics, 286(2), 1998, pp. 697-703
This study characterized the antinociceptive, respiratory and heart ra
te effects of the cannabinoid receptor agonists Delta-9-tetrahydrocann
abinol (Delta-9-THC) and WIN 55212 nyl)methyl]pyrol-[1,2,3-de]-1,4-ben
zoxazin-6-yl)(1 -naphtalenyl)methanone monomethanesulfonate}, N-arachi
donyl ethanolamide (anandamide) and the mu and kappa opioid receptor a
gonists heroin and U69593, alone and in conjunction with a cannabinoid
receptor antagonist, SR 141716A ichlorophenyl)-4-methyl-1H-pyrazole--
3-carboxamide hydrochioride] and an opioid receptor antagonist, quadaz
ocine, in rhesus monkeys (Macaca mulatta). Using 12 adult rhesus monke
ys, latencies to remove the tail from a 50 degrees C water bath, respi
ration in 5% CO2 and heart rate were measured. When administered alone
, SR 141716A (1.8, 5.6 mg/kg i.m.) did not alter nociception, respirat
ion or heart rate. Delta-9-THC (0.1-10 mg/kg i.m.) and WIN 55212 (0.1-
10 mg/kg i.m.) dose-dependently increased antinociception and dose-dep
endently decreased respiratory minute and tidal volumes and heart rate
. These antinociceptive, respiratory and heart rate effects were rever
sed by SR 141716A but not by the opioid antagonist quadazocine (1 mg/k
g i.m.). Anandamide (10 mg/kg i.m.) also produced antinociception. Her
oin (0.01-10 mg/kg i.m.) and U69593 (0.013.2 mg/kg i.m.) also dose-dep
endently increased antinociception and decreased respiratory and heart
rate measures; these effects were antagonized by quadazocine but not
by SR 141716A. These results demonstrate selective and reversible anta
gonism of cannabinoid behavioral effects by SR 141716A in rhesus monke
ys.