Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development

Research output: Contribution to journalLiterature review

181 Citations (Scopus)

Abstract

This review highlights some important advances that have taken place in cannabinoid research over the last four years. It focuses on novel ligands that are of interest either as experimental tools or as lead compounds for therapeutic agents and possible clinical applications for some of these ligands. The molecular targets for these compounds are various components of the system of endogenous cannabinoids (endocannabinoids) and receptors that together constitute the 'endocannabinoid system'. These are CB1 cannabinoid receptors that are present mainly on central and peripheral neurones, CB2 cannabinoid receptors that are expressed predominantly by immune cells, the biochemical mechanisms responsible for the tissue uptake or metabolism of endocannabinoids and vanilloid receptors. Other cannabinoid receptor types may also exist. Recently developed ligands include potent and selective agonists for CB1 and CB2 receptors, a potent CB2-selective antagonist/inverse agonist and inhibitors of endocannabinoid uptake or metabolism. Future research should be directed at characterising the endocannabinoid system more completely and at obtaining more conclusive clinical data about the possible beneficial effects of cannabinoids as well as their adverse effects. There is also a need for improved cannabinoid formulations/modes of administration in the clinic and advances in this area should be facilitated by the recent development of a potent water-soluble CB1/CB2 receptor agonist. A growing number of strategies for separating sought-after therapeutic effects of cannabinoid receptor agonists from the unwanted consequences of CB1 receptor activation are now emerging and these are discussed at the end of this review.

Original languageEnglish
Pages (from-to)1553-1571
Number of pages19
JournalExpert Opinion on Investigational Drugs
Volume9
Publication statusPublished - 2000

Keywords

  • ACEA
  • ACPA
  • AM374
  • AM381
  • AM404
  • AM630
  • anandamide
  • cannabinoid receptors
  • cannabinoid receptor agonists
  • cannabinoid receptor antagonists
  • endogenous cannabinoids
  • chronic pain
  • HU-308
  • JWH-133
  • LY320135
  • L-759633
  • L-759656
  • multiple sclerosis
  • O-1184
  • O-1057
  • SR141716A
  • SR144528
  • vanilloid receptors
  • MULTIPLE-SCLEROSIS
  • CB1 RECEPTORS
  • STRUCTURAL DETERMINANTS
  • INVERSE AGONIST
  • RAT-BRAIN
  • MESENTERIC VASODILATION
  • SELECTIVE-INHIBITION
  • ANANDAMIDE TRANSPORT
  • TOURETTES-SYNDROME
  • KNOCKOUT MICE

Cite this

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title = "Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development",
abstract = "This review highlights some important advances that have taken place in cannabinoid research over the last four years. It focuses on novel ligands that are of interest either as experimental tools or as lead compounds for therapeutic agents and possible clinical applications for some of these ligands. The molecular targets for these compounds are various components of the system of endogenous cannabinoids (endocannabinoids) and receptors that together constitute the 'endocannabinoid system'. These are CB1 cannabinoid receptors that are present mainly on central and peripheral neurones, CB2 cannabinoid receptors that are expressed predominantly by immune cells, the biochemical mechanisms responsible for the tissue uptake or metabolism of endocannabinoids and vanilloid receptors. Other cannabinoid receptor types may also exist. Recently developed ligands include potent and selective agonists for CB1 and CB2 receptors, a potent CB2-selective antagonist/inverse agonist and inhibitors of endocannabinoid uptake or metabolism. Future research should be directed at characterising the endocannabinoid system more completely and at obtaining more conclusive clinical data about the possible beneficial effects of cannabinoids as well as their adverse effects. There is also a need for improved cannabinoid formulations/modes of administration in the clinic and advances in this area should be facilitated by the recent development of a potent water-soluble CB1/CB2 receptor agonist. A growing number of strategies for separating sought-after therapeutic effects of cannabinoid receptor agonists from the unwanted consequences of CB1 receptor activation are now emerging and these are discussed at the end of this review.",
keywords = "ACEA, ACPA, AM374, AM381, AM404, AM630, anandamide, cannabinoid receptors, cannabinoid receptor agonists, cannabinoid receptor antagonists, endogenous cannabinoids, chronic pain, HU-308, JWH-133, LY320135, L-759633, L-759656, multiple sclerosis, O-1184, O-1057, SR141716A, SR144528, vanilloid receptors, MULTIPLE-SCLEROSIS, CB1 RECEPTORS, STRUCTURAL DETERMINANTS, INVERSE AGONIST, RAT-BRAIN, MESENTERIC VASODILATION, SELECTIVE-INHIBITION, ANANDAMIDE TRANSPORT, TOURETTES-SYNDROME, KNOCKOUT MICE",
author = "Pertwee, {R G}",
year = "2000",
language = "English",
volume = "9",
pages = "1553--1571",
journal = "Expert Opinion on Investigational Drugs",
issn = "1354-3784",
publisher = "Informa Healthcare",

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TY - JOUR

T1 - Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development

AU - Pertwee, R G

PY - 2000

Y1 - 2000

N2 - This review highlights some important advances that have taken place in cannabinoid research over the last four years. It focuses on novel ligands that are of interest either as experimental tools or as lead compounds for therapeutic agents and possible clinical applications for some of these ligands. The molecular targets for these compounds are various components of the system of endogenous cannabinoids (endocannabinoids) and receptors that together constitute the 'endocannabinoid system'. These are CB1 cannabinoid receptors that are present mainly on central and peripheral neurones, CB2 cannabinoid receptors that are expressed predominantly by immune cells, the biochemical mechanisms responsible for the tissue uptake or metabolism of endocannabinoids and vanilloid receptors. Other cannabinoid receptor types may also exist. Recently developed ligands include potent and selective agonists for CB1 and CB2 receptors, a potent CB2-selective antagonist/inverse agonist and inhibitors of endocannabinoid uptake or metabolism. Future research should be directed at characterising the endocannabinoid system more completely and at obtaining more conclusive clinical data about the possible beneficial effects of cannabinoids as well as their adverse effects. There is also a need for improved cannabinoid formulations/modes of administration in the clinic and advances in this area should be facilitated by the recent development of a potent water-soluble CB1/CB2 receptor agonist. A growing number of strategies for separating sought-after therapeutic effects of cannabinoid receptor agonists from the unwanted consequences of CB1 receptor activation are now emerging and these are discussed at the end of this review.

AB - This review highlights some important advances that have taken place in cannabinoid research over the last four years. It focuses on novel ligands that are of interest either as experimental tools or as lead compounds for therapeutic agents and possible clinical applications for some of these ligands. The molecular targets for these compounds are various components of the system of endogenous cannabinoids (endocannabinoids) and receptors that together constitute the 'endocannabinoid system'. These are CB1 cannabinoid receptors that are present mainly on central and peripheral neurones, CB2 cannabinoid receptors that are expressed predominantly by immune cells, the biochemical mechanisms responsible for the tissue uptake or metabolism of endocannabinoids and vanilloid receptors. Other cannabinoid receptor types may also exist. Recently developed ligands include potent and selective agonists for CB1 and CB2 receptors, a potent CB2-selective antagonist/inverse agonist and inhibitors of endocannabinoid uptake or metabolism. Future research should be directed at characterising the endocannabinoid system more completely and at obtaining more conclusive clinical data about the possible beneficial effects of cannabinoids as well as their adverse effects. There is also a need for improved cannabinoid formulations/modes of administration in the clinic and advances in this area should be facilitated by the recent development of a potent water-soluble CB1/CB2 receptor agonist. A growing number of strategies for separating sought-after therapeutic effects of cannabinoid receptor agonists from the unwanted consequences of CB1 receptor activation are now emerging and these are discussed at the end of this review.

KW - ACEA

KW - ACPA

KW - AM374

KW - AM381

KW - AM404

KW - AM630

KW - anandamide

KW - cannabinoid receptors

KW - cannabinoid receptor agonists

KW - cannabinoid receptor antagonists

KW - endogenous cannabinoids

KW - chronic pain

KW - HU-308

KW - JWH-133

KW - LY320135

KW - L-759633

KW - L-759656

KW - multiple sclerosis

KW - O-1184

KW - O-1057

KW - SR141716A

KW - SR144528

KW - vanilloid receptors

KW - MULTIPLE-SCLEROSIS

KW - CB1 RECEPTORS

KW - STRUCTURAL DETERMINANTS

KW - INVERSE AGONIST

KW - RAT-BRAIN

KW - MESENTERIC VASODILATION

KW - SELECTIVE-INHIBITION

KW - ANANDAMIDE TRANSPORT

KW - TOURETTES-SYNDROME

KW - KNOCKOUT MICE

M3 - Literature review

VL - 9

SP - 1553

EP - 1571

JO - Expert Opinion on Investigational Drugs

JF - Expert Opinion on Investigational Drugs

SN - 1354-3784

ER -