[Treatment of insomnia. Pharmacological approaches and their limitations].
Far more people complain of inadequate sleep than of true insomnia warranting prescription of a hypnotic drug. The number of available hypnotics has fallen markedly in recent years. Numerous brain areas, transmitters and receptors are involved in sleep. Currently, the main hypnotics (benzodiazepine derivatives and the so-called 4Z group. Zolpidem, Zopiclone, EsZopiclone and Zaleplon) increase GABAergic transmission by acting on components of chloride channels, thereby inducing Cl entry to neurons and resulting in their hyperpolarisation. This pre-eminence of GABAergic transmission should not make us ignore other important transmitters and their receptors as potential targets for new hypnotic drugs; these include histamine (and H1 receptors), dopamine (D1 and D2), norepinephrine (alpha1), serotonin (5HT2), glutamate (NMDA), acetylcholine (nicotinic), hypocretin (OX1 and OX2), melatonin (MLT1 and MLT2), prostaglandin E2 (EP), prostaglandin D2 (DP1), and endocannabinoids (CB1). Knowledge of the pharmacodynamic, pharmacokinetic and clinical characteristics of current hypnotic drugs has allowed us to establish the profile of an ideal hypnotic for the future.
Académie nationale de médecine. jeanhenri.costentin@orange.fr
Jean
J
Costentin
D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D011963:Receptors, GABA-A / Q000187:drug effects; D018080:Receptors, GABA-B / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*
D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B