Cited by 99Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsNeuropeptides and Animal Physiology

Analgesic, Respiratory and Heart Rate Effects of Cannabinoid and Opioid Agonists in Rhesus Monkeys: Antagonist Effects of SR 141716A

Vivian, Jeffrey A., Kishioka, Shiroh, Butelman, Eduardo R., Broadbear, Jillian, Lee, Katherine O., Woods, James H.·1998·The Journal of Pharmacology and Experimental Therapeutics

Abstract

This study characterized the antinociceptive, respiratory and heart rate effects of the cannabinoid receptor agonists Delta-9-tetrahydrocannabinol (Delta-9-THC) and WIN 55212 ((R)-(+)-2, 3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol-[1,2,3-de]-1, 4-benzoxazin-6-yl)(1-naphtalenyl)methanone monomethanesulfonate), N-arachidonyl ethanolamide (anandamide) and the mu and kappa opioid receptor agonists heroin and U69593, alone and in conjunction with a cannabinoid receptor antagonist, SR 141716A [N-(piperidin-1-1-yl)-5-(4-chlorophenyl)-1(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] and an opioid receptor antagonist, quadazocine, in rhesus monkeys (Macaca mulatta). Using 12 adult rhesus monkeys, latencies to remove the tail from a 50 degrees C water bath, respiration 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, respiration 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-dependently decreased respiratory minute and tidal volumes and heart rate. These antinociceptive, respiratory and heart rate effects were reversed by SR 141716A but not by the opioid antagonist quadazocine (1 mg/kg i.m.). Anandamide (10 mg/kg i.m.) also produced antinociception. Heroin (0.01-10 mg/kg i.m.) and U69593 (0.01-3.2 mg/kg i.m.) also dose-dependently 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 antagonism of cannabinoid behavioral effects by SR 141716A in rhesus monkeys.

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Crossref · 10.1016/s0022-3565(24)37642-6

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  • In the rhesus monkey warm water tail withdrawal paradigm, AEA, THC, and WIN55,212-2 produce dose-dependent antinociceptive effects.

    “In the rhesus monkey warm water tail withdrawal paradigm, the endogenous cannabinoid arachidonoylethanolamine (anandamide; AEA), the primary active constituent of cannabis Δ 9 -tetrahydrocannabinol (THC), and the high efficacy synthetic cannabinoid receptor agonist WIN55,212-2 produce dose-dependent antinociceptive effects (Manning et al, 2001;Vivian et al, 1998).”

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Authors
Vivian, J. A., Kishioka, S., Butelman, E. R., Broadbear, J., Lee, K. O., & Woods, J. H.
Affiliations
University of Michigan (US)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
1998-08
Volume
286
Issue
2
Pages
697-703
ISSN
0022-3565 (ISSN-L)
OpenAlex
W2101889344
Cited by
98
References
38
Citations by year
2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 5
FWCI
5.37
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Journal of Pharmacology and Experimental Therapeutics
Funders
National Institute on Drug Abuse (DA05773, DA-07268, T32DA007268, DA-00254)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
cannabinoid receptor agonists, opioid agonists, antinociception, analgesia, respiratory depression, heart rate, SR141716A, rimonabant, cannabinoid receptor antagonists, opioid antagonists, delta-9-tetrahydrocannabinol, anandamide, heroin, U69593
MeSH terms
Rimonabant, Analgesics, Opioid, Animals, Cannabinoids, Heroin, Dose-Response Relationship, Drug, Hallucinogens, Heart Rate, Macaca mulatta, Morpholines, Naphthalenes, Pain Measurement, Piperidines, Pyrazoles, Pyrrolidines, Receptors, Drug, Receptors, Opioid, Dronabinol, Respiratory Mechanics, Receptors, Cannabinoid, Benzeneacetamides, Benzoxazines

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