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Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice.
Eur J Pharmacol. 2006 Sep 28; 546(1-3):60-8.EJ

Abstract

The analgesic and anti-hyperalgesic effects of cannabinoid- and vanilloid-like compounds, plus the fatty acid amide hydrolase (FAAH) inhibitor Cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597), and acetaminophen, were evaluated in the phenyl-p-quinone (PPQ) pain model, using different routes of administration in combination with opioid and cannabinoid receptor antagonists. All the compounds tested produced analgesic effects. Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide) were active by three routes of administration: i.p., s.c. and, p.o. Delta(9)-THC produced ED(50)s of 2.2 mg/kg (0.3-15.6) i.p., 9 mg/kg (4.3-18.9) s.c., and 6.4 mg/kg (5.5-7.6) p.o. Similarly, (R)-methanandamide yielded ED(50)s of 2.9 mg/kg (1-8) i.p., 11 mg/kg (7-17) s.c., and 11 mg/kg (0.9-134) p.o. N-vanillyl-arachidonyl-amide (arvanil) was active by two routes, producing ED(50)s of 4.7 mg/kg (3.0-7.4) s.c. and 0.06 mg/kg (0.02-0.2) i.p. Palmitoylethanolamide, URB597, and acetaminophen were active i.p., resulting in ED(50)s of 3.7 mg/kg (3.2-4.2), 22.9 mg/kg (11.1-47.2), and 160 mg/kg (63-405), respectively. None of the cannabinoid or opioid receptor antagonists tested blocked the compounds evaluated, with two exceptions: the antinociceptive effects of Delta(9)-THC and URB597 were completely blocked by SR141716A, a cannabinoid CB(1) receptor antagonist. Western immunoassays performed using three opioid receptor antibodies, a cannabinoid CB(1) receptor antibody and a transient receptor potential vanilloid type 1(TRPV(1)) receptor antibody, yielded no change in receptor protein levels after short-term arvanil, (R)-methanandamide or Delta(9)-THC administration. These data suggest that all the compounds tested, except Delta(9)-THC and URB597, produced analgesia via a non-cannabinoid CB(1), non-cannabinoid CB(2) pain pathway not yet identified.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16919265

Citation

Haller, Victoria L., et al. "Non-cannabinoid CB1, Non-cannabinoid CB2 Antinociceptive Effects of Several Novel Compounds in the PPQ Stretch Test in Mice." European Journal of Pharmacology, vol. 546, no. 1-3, 2006, pp. 60-8.
Haller VL, Cichewicz DL, Welch SP. Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice. Eur J Pharmacol. 2006;546(1-3):60-8.
Haller, V. L., Cichewicz, D. L., & Welch, S. P. (2006). Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice. European Journal of Pharmacology, 546(1-3), 60-8.
Haller VL, Cichewicz DL, Welch SP. Non-cannabinoid CB1, Non-cannabinoid CB2 Antinociceptive Effects of Several Novel Compounds in the PPQ Stretch Test in Mice. Eur J Pharmacol. 2006 Sep 28;546(1-3):60-8. PubMed PMID: 16919265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice. AU - Haller,Victoria L, AU - Cichewicz,Diana L, AU - Welch,Sandra P, Y1 - 2006/07/25/ PY - 2006/04/05/received PY - 2006/06/28/revised PY - 2006/07/13/accepted PY - 2006/8/22/pubmed PY - 2007/1/12/medline PY - 2006/8/22/entrez SP - 60 EP - 8 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 546 IS - 1-3 N2 - The analgesic and anti-hyperalgesic effects of cannabinoid- and vanilloid-like compounds, plus the fatty acid amide hydrolase (FAAH) inhibitor Cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597), and acetaminophen, were evaluated in the phenyl-p-quinone (PPQ) pain model, using different routes of administration in combination with opioid and cannabinoid receptor antagonists. All the compounds tested produced analgesic effects. Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide) were active by three routes of administration: i.p., s.c. and, p.o. Delta(9)-THC produced ED(50)s of 2.2 mg/kg (0.3-15.6) i.p., 9 mg/kg (4.3-18.9) s.c., and 6.4 mg/kg (5.5-7.6) p.o. Similarly, (R)-methanandamide yielded ED(50)s of 2.9 mg/kg (1-8) i.p., 11 mg/kg (7-17) s.c., and 11 mg/kg (0.9-134) p.o. N-vanillyl-arachidonyl-amide (arvanil) was active by two routes, producing ED(50)s of 4.7 mg/kg (3.0-7.4) s.c. and 0.06 mg/kg (0.02-0.2) i.p. Palmitoylethanolamide, URB597, and acetaminophen were active i.p., resulting in ED(50)s of 3.7 mg/kg (3.2-4.2), 22.9 mg/kg (11.1-47.2), and 160 mg/kg (63-405), respectively. None of the cannabinoid or opioid receptor antagonists tested blocked the compounds evaluated, with two exceptions: the antinociceptive effects of Delta(9)-THC and URB597 were completely blocked by SR141716A, a cannabinoid CB(1) receptor antagonist. Western immunoassays performed using three opioid receptor antibodies, a cannabinoid CB(1) receptor antibody and a transient receptor potential vanilloid type 1(TRPV(1)) receptor antibody, yielded no change in receptor protein levels after short-term arvanil, (R)-methanandamide or Delta(9)-THC administration. These data suggest that all the compounds tested, except Delta(9)-THC and URB597, produced analgesia via a non-cannabinoid CB(1), non-cannabinoid CB(2) pain pathway not yet identified. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16919265/Non_cannabinoid_CB1_non_cannabinoid_CB2_antinociceptive_effects_of_several_novel_compounds_in_the_PPQ_stretch_test_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00754-0 DB - PRIME DP - Unbound Medicine ER -