5 Analgesics and their Antagonists: Biochemical Aspects and Structure-Activity Relationships

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This chapter discusses the many aspects of analgesics: (a) estimation of analgesics in biological media; (b) absorption, distribution and excretion of analgesics; (c) metabolism of analgesics; (d) antagonists of analgesics; (e) relation of morphine-type analgesics to adrenergic and cholinergic mechanisms, and other biochemical processes; and (f) structure–activity relationships. The chapter reports the pharmacology of N-allylnormorphine, an analogue of morphine in which the N-methyl group of the latter drug is replaced by an allyl group. It is well established that morphine causes a release of adrenaline; the adrenaline-depleting action of morphine upon the adrenal gland of cats and dogs. It reviews that acute administration of morphine produces an activation of sympathetic part of the nervous system that leads to a depletion of brain and adrenal stores of catecholamines in rats and cats, while chronic administration of the same drug induced an increased rate of resynthesis of catecholamines. It has been suggested that the analgesia produced by morphine-type analgesics is mediated, wholly or in part, through a release of adrenaline from the adrenal medulla. It is; therefore, evident that efforts to associate the analgesic properties of morphine with its effects upon functional systems within the body have so far been unsuccessful.

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