Recent Findings on the Mechanism of Action of Morphine: Implications for the Development of New Analgesics

Authors: Valverde O.1; Maldonado R.1; Kieffer B.L.2

Source: CNS Drugs, Volume 10, Number 1, July 1998 , pp. 1-10(10)

Publisher: Adis International

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Abstract:

Opioids exert their pharmacological actions through 3 types of receptors: µ, delta and kappa. Previous studies have suggested that all 3 opioid receptors are involved in several pharmacological responses induced by classical opioids such as morphine. The cloning of opioid receptors has provided new molecular tools to assist in delineating the contribution of each receptor type to the physiological and pharmacological responses induced by opioids.

Recently, we described the effects of morphine in mutant mice that lack opioid µ-receptors. Findings obtained in these mice on the analgesic and rewarding properties of, and physical dependence induced by, morphine have been compared with those previously reported from studies using classical pharmacological procedures. Taken together, these data indicate that the antinociception, rewarding effects and physical dependence produced by morphine are mediated exclusively by the stimulation of µ-receptors. Therefore, both analgesia and the main adverse effects derived from repeated administration of morphine are due to the activation of the same receptor type.

Future studies using µ-receptor-deficient mice and other genetically modified animal models will allow the clarification of the specific role that delta- and kappa- receptors play in the biological actions of opioids. This information could assist in developing more effective opioid analgesics that have fewer adverse effects than currently available agents.

Keywords: Reviews-on-treatment; Morphine, pharmacodynamics; Analgesics, pharmacodynamics; Pain; Dependence

Language: English

Document Type: Leading article

Affiliations: 1: Departement de Pharmacochimie Moléculaire, Université René Descartes, Paris, France 2: UPR 9050 CNRS, ESBS Université Louis Pasteur, Parc d'Innovation, Strasbourg, France *

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