Irreversible blockade of striatal dopamine receptors in vivo by a derivative of alpha-flupenthixol.

Flupenthixyl chloride (FPT-Cl), a derivative of the dopamine (DA) receptor antagonist and neuroleptic alpha-flupenthixol possessing a chloroethyl side chain, has been prepared and evaluated for use in vivo in affinity labeling of DA receptors. Binding of [3H]spiperone to rat striatal DA receptors was markedly altered up to 12 h after intraventricular injection of FPT-Cl as compared with controls, while Scatchard plots of [3H]spiperone binding obtained on rat striatal homogenates 24 and 48 h after injection of FPT-Cl had values of Bmax significantly lower than in controls. The results suggest that the administration of FPT-Cl leads to irreversible and possibly covalent blockade of a portion of the spiperone binding sites in rat striatum. A second population of receptors appears to be blocked reversibly and presumably noncovalently by FPT-Cl, and these spiperone binding sites are partially reactivated in vivo after 48 h.