Chlorpromazine HCl (Synonyms: CPZ)

Dopamine receptors are a class of G protein-coupled receptors that are prominent in the central nervous system. Dopamine receptors are implicated in many neurological processes. Thus, dopamine receptors are common neurologic drug targets. Antipsychotics are often dopamine receptor antagonists while typically psychostimulants are indirect agonists of dopamine receptors. Chlorpromazine is a dopamine antagonist.

In vitro: The antipsychotic activity of chlorpromazine has been associated with its ability to act as a dopamine-receptor antagonist. the manner in which chlorpromazine, with its phenothiazine ring structure, interacted with a receptor for dopamine. Furthermore, chlorpromazine inhibited the binding of [3H]spiperone, and the inhibition curve was consistent with a single class of binding sites [1].

In vivo: Daily administration of chlorpromazine to rats for 21 days induced catalepsy, tolerance to catalepsy and locomotor sensitization following PCP challenge. Results suggest that daily chlorpromazine treatment induced DA/NMDA-receptor sensitization to total locomotor activity following PCP challenge [2].

Clinical trial: Chlorpromazine is clinical used as a conventional antipsychotic drug that has been used for the management of psychotic disorders since its FDA approval in 1954.

Reference:
[1] Harrold MW, Chang YA, Wallace RA, Farooqui T, Wallace LJ, Uretsky N, Miller DD.  Charged analogues of chlorpromazine as dopamine antagonists. J Med Chem. 1987 Sep;30(9):1631-5.
[2] Nsimba SE.  Effects of daily chlorpromazine administration on behavioural and physiological parameters in the rat. Indian J Physiol Pharmacol. 2009 Jul-Sep;53(3):209-18.