TITLE

Mechanisms of Action of Antipsychotic Drugs of Different Classes, Refractoriness to Therapeutic Effects of Classical Neuroleptics, and Individual Variation in Sensitivity to their Actions: PART I

AUTHOR(S)
Miller, R.
PUB. DATE
December 2009
SOURCE
Current Neuropharmacology;Dec2009, Vol. 7 Issue 4, p302
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Many issues remain unresolved about antipsychotic drugs. Their therapeutic potency scales with affinity for dopamine D2 receptors, but there are indications that they act indirectly, with dopamine D1 receptors (and others) as possible ultimate targets. Classical neuroleptic drugs disinhibit striatal cholinergic interneurones and increase acetyl choline release. Their effects may then depend on stimulation of muscarinic receptors on principle striatal neurones (M4 receptors, with reduction of cAMP formation, for therapeutic effects; M1 receptors for motor side effects). Many psychotic patients do not benefit from neuroleptic drugs, or develop resistance to them during prolonged treatment, but respond well to clozapine. For patients who do respond, there is a wide (>ten-fold) range in optimal doses. Refractoriness or low sensitivity to antipsychotic effects (and other pathologies) could then arise from low density of cholinergic interneurones. Clozapine probably owes its special actions to direct stimulation of M4 receptors, a mechanism available when indirect action is lost.
ACCESSION #
52316489

 

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics