Beyond the serotonin reuptake inhibitors: rationales for the development of new serotonergic agents

Serotonin (5-HT) is a neurotransmitter involved in the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth, and appetitive functions. Medications that act on 5-HT and its receptors have applications in the treatment of a variety of psychiatric disorders, among them depression, anxiety, psychoses, eating disorders, obsessive compulsive disorder, body dysmorphic disorder, posttraumatic stress disorder, and conditions associated with aggression. The clinical effects of these medications depend not only on their capacity to increase synaptic concentrations of 5-HT, but also on their effects on subtypes of 5-HT receptors and on other neurotransmitter systems. A new generation of drugs acting on specific 5-HT receptors has the advantage of a low frequency of adverse effects, applicability in mixed and complicated syndromes, and usefulness as probes of the psychobiology of mental disorders. An understanding of the specific actions of these medications on cellular communication and signaling makes it easier to predict their applications and disadvantages in specific clinical syndromes. The diverse applications of this new generation of drugs suggest a reconceptualization of the categorical approach to diagnosis and the addition of a more dimensional approach, at least to psychopharmacology.