All antipsychotic drugs
tend to block D2 receptors in the dopamine pathways of the brain.
This means that dopamine released in these pathways has less effect. Excess
release of dopamine in the mesolimbic pathway has been linked to psychotic
experiences. It has also been proven[citation needed] less
dopamine released in the prefrontal cortex in the brain, and excess dopamine
released from all other pathways, has also been linked to psychotic
experiences, caused by abnormal dopaminergic function as a result of patients
suffering from schizophrenia or bipolar disorder.
Various neuroleptics such as
haloperidol and chlorpromazine suppress dopamine chemicals throughout its
pathways, in order for dopamine receptors to function normally. Typical antipsychotics
are not particularly selective and also block dopamine receptors in the
mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal
pathway. Blocking D2 receptors in these other pathways is thought to
produce some of the unwanted side effects that the typical antipsychotics can
produce. They were commonly classified on a spectrum of low potency to high
potency, where potency referred to the ability of the drug to bind to dopamine
receptors, and not to the effectiveness of the drug. High-potency
antipsychotics such as haloperidol, in general, have doses of a few milligrams
and cause less sleepiness and calming effects than low-potency antipsychotics
such as chlorpromazine and thioridazine, which have dosages of several hundred
milligrams. The latter have a greater degree of anticholinergic and
antihistaminergic activity, which can counteract dopamine-related side effects.
Atypical antipsychotic drugs have
a similar blocking effect on D2 receptors. Some also block or
partially block serotonin receptors (particularly 5HT2A, C and 5HT1A
receptors):ranging from risperidone, which acts overwhelmingly on serotonin
receptors, to amisulpride, which has no serotonergic activity. The additional
effects on serotonin receptors may be why some of them can benefit the
"negative symptoms" of schizophrenia.(Murphy et al., 2006)
Fig. 1: Diagram showing the Mechanism of action of antipsychotic (Katzung et al., 2001)