PMID: 9180828Apr 1, 1997Paper

The neurobiology and pharmacology of depression. A comparative overview of serotonin selective antidepressants

South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde
B H Harvey

Abstract

Over the past decade, targeted drug design has led to significant advances in the pharmacological management of depression. A serendipitous approach to drug discovery has therefore been replaced by the development of drugs acting on predetermined neurobiological targets recognised to be involved in the pathology of depressive illness. The first of these 'designer drugs', were the selective serotonin (5-HT) re-uptake inhibitors (SSRIs), followed more recently by venlafaxine and nefazodone which, in addition to 5-HT uptake, also target noradrenaline (NA) uptake and 5-HT2 receptors, respectively. This paper reviews the biochemistry and pharmacology of depression. From this foundation, the relevance of 5-HT selectivity is discussed followed by a comparison of the clinical pharmacology and pharmacokinetics of 5-HT-selective antidepressants. Despite their common action on synaptic 5-HT uptake, structural heterogeneity among the group allows differences to be observed in kinetic and pharmacological parameters, viz. plasma half-life (T1/2), liver metabolism, protein binding, receptor affinities and selectivity ratios. This not only leeds to different attributes which assist in the successful management of a particular patient, but will...Continue Reading

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