Pharmacology of cannabinoid receptor ligands

Research output: Contribution to journalLiterature review

419 Citations (Scopus)

Abstract

Mammalian tissues contain at least two types of cannabinoid receptor, CB1 and CB2, both coupled to G proteins. CB1 receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB2 receptors occur in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this 'endogenous cannabinoid system' has been paralleled by a renewed interest in possible therapeutic applications of cannabinoids, for example in the management of pain and in the suppression of muscle spasticity/spasm associated with multiple sclerosis or spinal cord injury. It has also prompted the development of a range of novel cannabinoid receptor ligands, including several that show marked selectivity for CB1 or CB2 receptors. This review summarizes current knowledge about the in vitro pharmacological properties of important CB1 and CB2 receptor ligands. Particular attention is paid to the binding properties of these ligands, to the efficacies of cannabinoid receptor agonists, as determined using cyclic AMP or [S-35]GTP gamma S binding assays, and to selected examples of how these pharmacological properties can be influenced by chemical structure. The in vitro pharmacological properties of ligands that can potently and selectively oppose the actions of CB1 or CB2 receptor agonists are also described. When administered by themselves, some of these ligands produce effects in certain tissue preparations that are opposite in direction to those produced by cannabinoid receptor agonists and the possibility that the ligands producing such 'inverse cannabimimetic effects' are inverse agonists rather than pure antagonists is discussed.

Original languageEnglish
Pages (from-to)635-664
Number of pages30
JournalCurrent Medicinal Chemistry
Volume6
Publication statusPublished - 1999

Keywords

  • ANTAGONIST SR 141716A
  • HIPPOCAMPAL ACETYLCHOLINE-RELEASE
  • ADENYLATE-CYCLASE INHIBITION
  • MEDIATED SIGNAL-TRANSDUCTION
  • ACTIVATED PROTEIN-KINASE
  • RAT CEREBELLAR MEMBRANES
  • LONG-TERM POTENTIATION
  • PIG SMALL-INTESTINE
  • CB1 RECEPTOR
  • BINDING-SITES

Cite this

Pharmacology of cannabinoid receptor ligands. / Pertwee, R G .

In: Current Medicinal Chemistry, Vol. 6, 1999, p. 635-664.

Research output: Contribution to journalLiterature review

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JO - Current Medicinal Chemistry

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