Neuropharmacologic and Behavioral Actions of Clonidine: Interactions With Central Neurotransmitters

Abstract

Publisher Summary The discovery of the antipsychotic action of chlorpromazine in the early 1950s and its usage in the treatment of schizophrenia heralded the beginning of modern psychopharmacology. Inquiries into the mechanism of action of this important compound led to the dopamine hypothesis of schizophrenia, a tenet that continues to provide one of the few durable models of brain dysfunction. This chapter focuses on the mechanism(s) by which clonidine produces its prominent pharmacological actions. Clonidine and related drugs may continue to be examined for potential antidementia effects. Despite the disappointing initial results in Alzheimer's patients, clonidine may exhibit beneficial actions in certain categories of human dementia. The possibility that combined treatment with clonidine and physostigmine may produce an added benefit fits with the observation of multiple neurotransmitter alterations in Alzheimer's disease. Several studies indicate that clonidine can inhibit many of the pharmacological effects produced by cholinesterase inhibitors, but this does not imply incompatibility for their use in dementia. A combination of physostigmine and clonidine is required to restore the beneficial effects of central cholinergic stimulation in the lesioned animals.