A novel long-lasting dopamine receptor blocker: haloperidol-bovine serum albumin conjugate.

The present study was undertaken in order to develop a long-lasting antagonist of dopamine receptors with a technique applicable to other molecules. Haloperidol was immobilized on a macromolecular backbone (bovine serum albumin) with a coupling ratio of 14 molecules haloperidol per molecule of bovine serum albumin. The long-lasting blockade of dopamine receptor activity was evaluated with the d-amphetamine-induced rotation model in rats. Unilateral intracerebral infusion of the conjugate into the caudate nucleus induced a blockade of dopamine receptors which lasted more than six days. The conjugate was able to trigger a greater amphetamine-induced rotation rate then haloperidol alone. This ipsilateral rotation appeared after doses of conjugate lower than those needed for unilateral haloperidol intracaudate infusion. This compound will enable the reversible blockade of dopaminergic transmission in a restricted area of the brain (diffusion of the conjugate was studied in detail) over a period of time needed for a behavioural study without the drawbacks of chemical or mechanical lesions.