Dopamine receptor occupancy in vivo: measurement using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)

N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) inactivates a variety of monoamine neurotransmitter receptors. In this report, protection against EEDQ-induced inactivation of D-1 and D-2 DA receptors by DA antagonists and agonists was used to obtain a measure of occupancy of these receptors in vivo by such drugs. Rats were pretreated with drugs and then given EEDQ (10 mg/kg, i.p.). Twenty-four hours after the EEDQ injections, the animals were decapitated and the number of receptors remaining was measured using conventional receptor binding assays. The D-1 antagonist SCH 23390 potently protected D-1 sites from EEDQ-induced inactivation in a dose-dependent manner. Similarly, NO-756, another D-1 antagonist, selectively protected D-1 sites from inactivation. Conversely, haloperidol, a relatively selective D-2 antagonist, protected D-2 sites from inactivation. Likewise, a number of antipsychotic DA antagonists also protected D-2 sites from inactivation. Clozapine, fluperlapine, and (+) butaclamol were effective at protecting both D-1 sites and D-2 sites. In addition, the D-1 agonist SKF 38393 protected D-1 sites from EEDQ-induced inactivation, whereas the D-2 agonist quinpirole protected D-2 sites. (-) Apomorphine, a mixed D-1/D-2 agonist, protected both sites. Thus, this type of method provides a simple means of evaluating the occupation of DA receptors by DA antagonists and agonists in vivo.