The effect of the dopamine receptor blocking drug pimozide on the stimulant and anorectic actions of dextroamphetamine in man

Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data

“…If the amphetamine cue is related to subjective effects in humans, similar agents should also block amphetamine-induced euphoria. However, in most studies the D 2 antagonist, pimozide, did not block amphetamine-induced euphoria in humans (Silverstone et al 1980;Jacobs and Silverstone 1986;de Wit 1995, 1996a,b), and the mixed D 1 /D 2 antagonist, fluphenazine, also failed to block these effects (Brauer and de Wit 1995). Similarly, if the discriminative stimulus effects of amphetamine are related to its euphorigenic effects, then D 2 agonists and some DA uptake inhibitors should mimic the subjective effects of amphetamine.…”

“…Few studies have examined the role of DA in amphetamine's effects in humans. These studies, most of which have examined interactions between amphetamine and antagonists, do not consistently support a primary role for DA (Gunne et al 1972;Jonsson 1972;Silverstone et al 1980;Nurnberger et al 1984;Jacobs and Silverstone 1986;de Wit 1995, 1996a,b). The reasons for the apparent discrepancies between the findings with laboratory animals and humans are not clear.…”

PET Study of [18F]6-Fluoro-l-Dopa Uptake in Neuroleptic- and Mood-Stabilizer-Naive First-Episode Nonpsychotic Mania: Effects of Treatment With Divalproex Sodium

“…For example, amphetamine, a psychostimulant, produces euphoria and other behavioral effects that are very similar to mania (1-3); these responses can be blocked by dopamine antagonists (4)(5)(6)(7). There is evidence that dextroamphetamine-induced arousal and euphoria in humans is mediated by a dopaminergic mechanism, as it is blocked by the selective dopamine blocker pimozide (8). Administration of drugs that increase dopamine transmission, such as L-dopa, d-amphetamine, piribedil, and bromocriptine, has been reported to precipitate mania in patients with bipolar depression (9)(10)(11)(12)(13)(14).…”

The Action of Stimulant Medication in Attention Deficit Disorder with Hyperactivity: Dopaminergic, Noradrenergic, or Both?

“…For example, Silverstone et al (1980) found that pimozide, a DA receptor-blocking drug, attenuated the centrally arousing effects of amphetamines in adult volunteers. In contrast, pimozide had no effects on dextroamphetamine-induced anorexia, suggesting that DA transmission did not mediate the anorectic action of amphetamine.…”