Pharmacological characterization of three novel cannabinoid receptor agonists in the mouse isolated vas deferens

Roger Guy Pertwee, G GRIFFIN, J A H LAINTON, J W HUFFMAN

Research output: Contribution to journalArticle

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Abstract

The novel compounds, 1-pentyl-2-methyl-3-(1-naphthoyl)indole, 1-pentyl-3-(1-naphthoyl)pyrrole and 1-heptyl-3-(1-naphthoyl)indole, produced a dose-related inhibition of electrically evoked contractions of the mouse vas deferens, with IC50 values of 2.56 nM, 3.38 nM and 639 nM respectively. K-d values of the selective CB1 cannabinoid receptor antagonist, SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxamide hydrochloride], determined in the vas deferens from experiments with these compounds are 1.34 nM, 3.86 nM and 8.06 nM respectively, indicating their susceptibility to antagonism by SR141716A is similar to that of their parent compound, the CB, cannabinoid receptor agonist WIN 55,212-2 {(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinomethyl][pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone}. SR141716A (100 nM) had no effect on the actions of two non-cannabinoid receptor agonists, morphine and clonidine. These results provide strong support for the hypothesis that 1-pentyl-2-methyl-3-(1-naphthoyl)indole, 1-pentyl-3(1-naphthoyl)pyrrole and 1-heptyl-3-(1-naphthoyl)indole are cannabinoid receptor agonists and confirm that the WIN 55,212-2 molecule can be modified considerably without detectable loss of cannabinoid activity.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalEuropean Journal of Pharmacology
Volume284
Issue number3
DOIs
Publication statusPublished - 25 Sep 1995

Keywords

  • CANNABINOID
  • CANNABINOID RECEPTOR ANTAGONIST
  • SR141716A
  • VAS DEFERENS, MOUSE
  • 1-PENTYL-2-METHYL-3-(1-NAPHTHOYL)INDOLE
  • 1-PENTYL-3-(1-NAPHTHOYL)PYRROLE
  • 1-HEPTYL-3-(1-NAPHTHOYL)INDOLE
  • Cannabinoid
  • Cannabinoid receptor antagonist
  • Vas deferens
  • mouse
  • 1-Pentyl-2-methyl-3-(1-naphthoyl)indole

Cite this

Pharmacological characterization of three novel cannabinoid receptor agonists in the mouse isolated vas deferens . / Pertwee, Roger Guy; GRIFFIN, G ; LAINTON, J A H ; HUFFMAN, J W .

In: European Journal of Pharmacology, Vol. 284, No. 3, 25.09.1995, p. 241-247.

Research output: Contribution to journalArticle

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AB - The novel compounds, 1-pentyl-2-methyl-3-(1-naphthoyl)indole, 1-pentyl-3-(1-naphthoyl)pyrrole and 1-heptyl-3-(1-naphthoyl)indole, produced a dose-related inhibition of electrically evoked contractions of the mouse vas deferens, with IC50 values of 2.56 nM, 3.38 nM and 639 nM respectively. K-d values of the selective CB1 cannabinoid receptor antagonist, SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxamide hydrochloride], determined in the vas deferens from experiments with these compounds are 1.34 nM, 3.86 nM and 8.06 nM respectively, indicating their susceptibility to antagonism by SR141716A is similar to that of their parent compound, the CB, cannabinoid receptor agonist WIN 55,212-2 {(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinomethyl][pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone}. SR141716A (100 nM) had no effect on the actions of two non-cannabinoid receptor agonists, morphine and clonidine. These results provide strong support for the hypothesis that 1-pentyl-2-methyl-3-(1-naphthoyl)indole, 1-pentyl-3(1-naphthoyl)pyrrole and 1-heptyl-3-(1-naphthoyl)indole are cannabinoid receptor agonists and confirm that the WIN 55,212-2 molecule can be modified considerably without detectable loss of cannabinoid activity.

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