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Characterization of the antinociceptive properties of cimetidine and a structural analog.
J Pharmacol Exp Ther. 1996 Feb; 276(2):500-8.JP

Abstract

The antinociceptive and pharmacological properties of the H2 receptor antagonist cimetidine and a novel cimetidine analog, SKF92374, were characterized. On both the hot-plate and tail-flick nociceptive tests, cimetidine and SKF92374 induced complete, dose-related analgesic responses when injected into the lateral ventricle of rats. SKF92374 showed strong similarities to cimetidine in analgesic efficacy, slope of dose-response curves and chemical structure, suggesting that these compounds share a common analgesic mechanism. In contrast, histamine induced submaximal antinociceptive effects, and the H3 antagonist thioperamide, a known HA-releasing drug, had little or no analgesic effects. Compared with cimetidine, SKF92374 showed very weak activity (400-fold lower affinity) on H2 receptors in vitro (isolated guinea pig atrium) and in vivo (rat gastric secretion). In addition, SKF92374 (100 microM) had neither agonist nor antagonist action on guinea pig ileum H1 receptors. SKF92374 was also a weak competitive antagonist of N alpha-methylhistamine-induced inhibition of electrically induced contractions of the guinea pig ileum (Kd = 5.2 microM), an H3 receptor-mediated response. Autoradiographic binding assays in guinea pig brain confirmed a weak antagonism of H3 receptors by SKF92374. The compound (up to 10 microM) also had no effect on unpurified rat brain histamine N-methyltransferase activity. These results support the hypothesis that cimetidine induces analgesia by a novel brain mechanism unrelated to H1, H2 or H3 receptors.

Authors+Show Affiliations

Department of Pharmacology and Neuroscience, Albany Medical College, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8632315

Citation

Li, B Y., et al. "Characterization of the Antinociceptive Properties of Cimetidine and a Structural Analog." The Journal of Pharmacology and Experimental Therapeutics, vol. 276, no. 2, 1996, pp. 500-8.
Li BY, Nalwalk JW, Barker LA, et al. Characterization of the antinociceptive properties of cimetidine and a structural analog. J Pharmacol Exp Ther. 1996;276(2):500-8.
Li, B. Y., Nalwalk, J. W., Barker, L. A., Cumming, P., Parsons, M. E., & Hough, L. B. (1996). Characterization of the antinociceptive properties of cimetidine and a structural analog. The Journal of Pharmacology and Experimental Therapeutics, 276(2), 500-8.
Li BY, et al. Characterization of the Antinociceptive Properties of Cimetidine and a Structural Analog. J Pharmacol Exp Ther. 1996;276(2):500-8. PubMed PMID: 8632315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the antinociceptive properties of cimetidine and a structural analog. AU - Li,B Y, AU - Nalwalk,J W, AU - Barker,L A, AU - Cumming,P, AU - Parsons,M E, AU - Hough,L B, PY - 1996/2/1/pubmed PY - 1996/2/1/medline PY - 1996/2/1/entrez SP - 500 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 276 IS - 2 N2 - The antinociceptive and pharmacological properties of the H2 receptor antagonist cimetidine and a novel cimetidine analog, SKF92374, were characterized. On both the hot-plate and tail-flick nociceptive tests, cimetidine and SKF92374 induced complete, dose-related analgesic responses when injected into the lateral ventricle of rats. SKF92374 showed strong similarities to cimetidine in analgesic efficacy, slope of dose-response curves and chemical structure, suggesting that these compounds share a common analgesic mechanism. In contrast, histamine induced submaximal antinociceptive effects, and the H3 antagonist thioperamide, a known HA-releasing drug, had little or no analgesic effects. Compared with cimetidine, SKF92374 showed very weak activity (400-fold lower affinity) on H2 receptors in vitro (isolated guinea pig atrium) and in vivo (rat gastric secretion). In addition, SKF92374 (100 microM) had neither agonist nor antagonist action on guinea pig ileum H1 receptors. SKF92374 was also a weak competitive antagonist of N alpha-methylhistamine-induced inhibition of electrically induced contractions of the guinea pig ileum (Kd = 5.2 microM), an H3 receptor-mediated response. Autoradiographic binding assays in guinea pig brain confirmed a weak antagonism of H3 receptors by SKF92374. The compound (up to 10 microM) also had no effect on unpurified rat brain histamine N-methyltransferase activity. These results support the hypothesis that cimetidine induces analgesia by a novel brain mechanism unrelated to H1, H2 or H3 receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8632315/Characterization_of_the_antinociceptive_properties_of_cimetidine_and_a_structural_analog_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8632315 DB - PRIME DP - Unbound Medicine ER -