AM630, a competitive cannabinoid receptor antagonist

Roger Guy Pertwee, Graeme Griffin, Susanthi Fernando, Xiuyan Li, Adam Hill, Alexandros Makriyannis

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

AM630 (iodopravadoline), a novel aminoalkylindole, has been found to attenuate the ability of a number of cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens. It did not block the inhibitory effects of morphine or clonidine on the twitch response. AM630 behaved as a competitive antagonist of CP 55,940, WIN 55,212-2, anandamide and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (AM356), producing rightward shifts in the log concentration response curves of these cannabinoid receptor agonists that were concentration-dependent, essentially parallel and not accompanied by any decrease in the size of maximal response. AM630 also produced concentration-dependent, parallel rightward shifts in the log concentration-response curve of Delta(9)-THC. However, these shifts were accompanied by a decrease in the maximal response. AM630 was markedly more potent as an antagonist of Delta(9)-THC and CP 55,940 (K-d = 14.0 and 17.3 nM respectively) than as an antagonist of WIN 55,212-2, AM356 or anandamide (K-d = 36.5, 85.9 and 278.8 nM respectively). These differences in dissociation constant imply that the mouse vas deferens may contain more than one type of cannabinoid receptor. The data also indicate that the receptors for which AM630 has the highest affinity may not be CB1 cannabinoid receptors as the CB1 selective antagonist, SR141716A, is known to be equally potent in attenuating the inhibitory effects of CP 55,940 and anandamide on the twitch response of the mouse vas deferens.

Original languageEnglish
Pages (from-to)1949-1955
Number of pages7
JournalLife Sciences
Volume56
Issue number23-24
DOIs
Publication statusPublished - 5 May 1995

Keywords

  • IODOPRAVADOLINE
  • CANNABINOID RECEPTOR ANTAGONIST
  • VAS DEFERENS
  • iodopravadoline
  • cannabinoid receptor antagonist
  • vas deferens

Cite this

Pertwee, R. G., Griffin, G., Fernando, S., Li, X., Hill, A., & Makriyannis, A. (1995). AM630, a competitive cannabinoid receptor antagonist . Life Sciences, 56(23-24), 1949-1955. https://doi.org/10.1016/0024-3205(95)00175-6

AM630, a competitive cannabinoid receptor antagonist . / Pertwee, Roger Guy; Griffin, Graeme; Fernando, Susanthi; Li, Xiuyan; Hill, Adam; Makriyannis, Alexandros.

In: Life Sciences, Vol. 56, No. 23-24, 05.05.1995, p. 1949-1955.

Research output: Contribution to journalArticle

Pertwee, RG, Griffin, G, Fernando, S, Li, X, Hill, A & Makriyannis, A 1995, 'AM630, a competitive cannabinoid receptor antagonist ', Life Sciences, vol. 56, no. 23-24, pp. 1949-1955. https://doi.org/10.1016/0024-3205(95)00175-6
Pertwee RG, Griffin G, Fernando S, Li X, Hill A, Makriyannis A. AM630, a competitive cannabinoid receptor antagonist . Life Sciences. 1995 May 5;56(23-24):1949-1955. https://doi.org/10.1016/0024-3205(95)00175-6
Pertwee, Roger Guy ; Griffin, Graeme ; Fernando, Susanthi ; Li, Xiuyan ; Hill, Adam ; Makriyannis, Alexandros. / AM630, a competitive cannabinoid receptor antagonist . In: Life Sciences. 1995 ; Vol. 56, No. 23-24. pp. 1949-1955.
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AU - Pertwee, Roger Guy

AU - Griffin, Graeme

AU - Fernando, Susanthi

AU - Li, Xiuyan

AU - Hill, Adam

AU - Makriyannis, Alexandros

PY - 1995/5/5

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N2 - AM630 (iodopravadoline), a novel aminoalkylindole, has been found to attenuate the ability of a number of cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens. It did not block the inhibitory effects of morphine or clonidine on the twitch response. AM630 behaved as a competitive antagonist of CP 55,940, WIN 55,212-2, anandamide and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (AM356), producing rightward shifts in the log concentration response curves of these cannabinoid receptor agonists that were concentration-dependent, essentially parallel and not accompanied by any decrease in the size of maximal response. AM630 also produced concentration-dependent, parallel rightward shifts in the log concentration-response curve of Delta(9)-THC. However, these shifts were accompanied by a decrease in the maximal response. AM630 was markedly more potent as an antagonist of Delta(9)-THC and CP 55,940 (K-d = 14.0 and 17.3 nM respectively) than as an antagonist of WIN 55,212-2, AM356 or anandamide (K-d = 36.5, 85.9 and 278.8 nM respectively). These differences in dissociation constant imply that the mouse vas deferens may contain more than one type of cannabinoid receptor. The data also indicate that the receptors for which AM630 has the highest affinity may not be CB1 cannabinoid receptors as the CB1 selective antagonist, SR141716A, is known to be equally potent in attenuating the inhibitory effects of CP 55,940 and anandamide on the twitch response of the mouse vas deferens.

AB - AM630 (iodopravadoline), a novel aminoalkylindole, has been found to attenuate the ability of a number of cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens. It did not block the inhibitory effects of morphine or clonidine on the twitch response. AM630 behaved as a competitive antagonist of CP 55,940, WIN 55,212-2, anandamide and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (AM356), producing rightward shifts in the log concentration response curves of these cannabinoid receptor agonists that were concentration-dependent, essentially parallel and not accompanied by any decrease in the size of maximal response. AM630 also produced concentration-dependent, parallel rightward shifts in the log concentration-response curve of Delta(9)-THC. However, these shifts were accompanied by a decrease in the maximal response. AM630 was markedly more potent as an antagonist of Delta(9)-THC and CP 55,940 (K-d = 14.0 and 17.3 nM respectively) than as an antagonist of WIN 55,212-2, AM356 or anandamide (K-d = 36.5, 85.9 and 278.8 nM respectively). These differences in dissociation constant imply that the mouse vas deferens may contain more than one type of cannabinoid receptor. The data also indicate that the receptors for which AM630 has the highest affinity may not be CB1 cannabinoid receptors as the CB1 selective antagonist, SR141716A, is known to be equally potent in attenuating the inhibitory effects of CP 55,940 and anandamide on the twitch response of the mouse vas deferens.

KW - IODOPRAVADOLINE

KW - CANNABINOID RECEPTOR ANTAGONIST

KW - VAS DEFERENS

KW - iodopravadoline

KW - cannabinoid receptor antagonist

KW - vas deferens

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DO - 10.1016/0024-3205(95)00175-6

M3 - Article

VL - 56

SP - 1949

EP - 1955

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

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ER -