Chapter 2 Antipsychotic Agents and Dopamine Agonists

This chapter summarizes the effective results of neuroleptic (antipsychotic) drugs in symptomatic treatment of schizophrenia, whose etiologies are unknown and may not be identical. This review begins with the recent discoveries about dopamine (DA) receptors. From the identification of DA receptors at the biochemical level, it has become clear that heterogeneity of DA receptors exists. Kainic acid injection into the striatum destroys striatal neurons, on which postsynaptic DA receptors are located while sparing axons that pass through this region and terminals that end within it. The bovine parathyroid gland is a tissue with a relatively homogeneous population of D-1 (cyclase-linked) receptors. In this tissue, DA stimulates the accumulation of cyclic adenosine monophosphate (c-AMP) and this event is followed by the release of parathyroid hormone from the gland. Apomorphine (APO) acts as a pure antagonist in this system. It appears that haloperidol and the other classical neuroleptics block both types of DA receptors. It is a corollary of the DA hypothesis of schizophrenia that pharmacological screening methods for antipsychotics are usually designed to discover DA blocking agents. Neuroleptics typically increase DA turnover, elevate prolactin levels, compete with DA receptor ligands for membrane binding sites, induce catalepsy, and block conditioned avoidance responding (CAR) in trained animals. Amoxapine that was previously known as a clinically effective antidepressant has now been shown by a Lederle group to have significant neuroleptic activity in a number of animal models. Nomifensin is an antidepressant that produces significant DA-mimetic motor effects in animal models. The ergot alkaloids have generally complex pharmacological profiles, but some with DA agonist properties are therapeutically useful.