Chapter 5. Antidepressants

Abstract

Publisher Summary Although reviews on neuropeptides, neurotransmitter precursors, and hormones as antidepressants (ADs) have appeared, the role of neurotransmitter amines in depression has remained a central theme. The pharmaco-electro-encephalography (EEC) profiles of ADs have been discussed in the chapter. Although numerous new chemical entities are predicted to be ADs based upon the findings in animals and human, the final verdict as to whether such agents are truly advances must await results from extensive, carefully controlled clinical trials. The clinical use, toxicity, and continuation and maintenance therapy of some established tricyclic compounds (TCAs), such asamoxapine, trimipramine, maprotiline, mianserin, and dimexiptiline are extensively studied. Amitriptyline- n -oxide is shown in clinical trial to give a more rapid improvement with less severe side effects than amitriptyline and imipramine. The solution conformation of the alkylamino side chain in a series of polycyclic amitriptyline analogs is found to be folded toward the polycyclic rings with the positively charged nitrogen situated above an aromatic ring. Several mianserin analogs are studied whose clinical evaluation might clarify the role of antagonism and concomitant NE uptake inhibition in mianserin's mode of AD activity. They could also provide a test of the AD predictive value of human EEC studies.