Smithkline Beecham Prize for Young Psychopharmacologists

Abstract

The symptoms and etiology of most major psychiatric disorders probably represent an underlying disturbance of neurotransmitter function. Understanding the mechanisms which control neurotransmitter function, and in particular neurotransmitter release, is therefore of considerable importance in determining the appropriate pharmacological treatment for these disorders. Calcium entry into neurons triggers the release of a wide range of neurotransmitters and recently our understanding of the mechanisms which control neuronal calcium entry has increased considerably. Neuronal calcium entry occurs through either voltage-sensitive or receptor-operated calcium channels. This article reviews the different subtypes of calcium channel, with particular reference to their structure; drugs which act upon them; and the possible function of the subtypes identified to date. In addition, it reviews the potential role of calcium channel antagonists in the treatment of a wide range of psychiatric disorders, and concludes that these drugs may have an increasing therapeutic role particularly in the treatment of drug dependence, mood disorders and Alzheimer's disease.

β-Phenylethylamines and the isoquinoline alkaloids

“…A synthesis of homocephalotaxine (262), a ring homologue of cephalotaxine not so far found occurring naturally, has been achieved from the tricyclic lactam (258). This was cyclized to [(259), R = SMe], desulfurized to [(259), R = HI, oxidized to the diol (260), and then to the diketone [(261), R = HI, the enol methyl ether of which [(261), R = Me] gave (262) on reduction.404…”