PNU-99,194(A) (or U-99,194(A)) is a drug which acts as a moderately selective D3 receptor antagonist with ~15-30-fold preference for D3 over the D2 subtype.

[1][2][3] Though it has substantially greater preference for D3 over D2, the latter receptor does still play some role in its effects, as evidenced by the fact that PNU-99,194 weakly stimulates both prolactin secretion and striatal dopamine synthesis, actions it does not share with the more selective (100-fold) D3 receptor antagonists S-14,297 and GR-103,691.

[4] In rodent studies, low doses of PNU-99,194 produce conditioned place preference (CPP) with no effect on intracranial self-stimulation (ICSS), whereas low doses of D3 agonists like 7-OH-DPAT inhibit ICSS behavior and cause conditioned place aversion (CPA).

[8][11] Other effects of PNU-99,194 at low doses in rodents include increased nociceptive responses,[12] hypothermia,[4][13] anxiolysis,[14] and facilitation of learning and memory,[12][15][16][17] as well as augmentation and inhibition, respectively, of amphetamine-induced reward and behavioral sensitization,[18][19] and reversal of morphine-induced CPP.

[6] At high doses it inhibits the self-administration of cocaine in both rats and monkeys.