Histamine

In a certain way, histaminergic systems have had a great, although indirect, historical importance in the development of neuropsychopharmacology. Indeed, the discovery of both the neuroleptic agents and the tricyclic antidepressant drugs in the 1950s was derived from the clinical study of behav-ioral actions of ‘‘antihistamines,’ ’ a class of antiallergic drugs now designated H1-receptor antagonists. Nevertheless, the histaminergic neuronal system in the brain, although already understood by the mid-1970s, has remained largely unexploited in drug design. Thus, only the traditional brain-penetrating H1-receptor antagonists, used as over-the-counter sleeping pills, are known to interfere with histaminergic transmissions in the central nervous sys-tem (CNS). This situation contrasts with the emergence, in the 1990s, of detailed knowledge of the system that re-vealed that it shares many biological and functional proper-ties with other aminergic systems overexploited in CNS drug design. Histamine and its receptors in the brain have been the subject of two comprehensive reviews (1,2). Therefore, to limit the length of the present chapter, we have deliberately elected to summarize the detailed information that can be found in these reviews and have added only more recent information and major references