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| Routes of administration | Oral |
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| Formula | C17H27NO2 |
| Molar mass | 277.408 g·mol−1 |
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PNU-99,194(A) (orU-99,194(A)) is adrug of the2-aminoindane family which acts as a moderatelyselectiveD3 receptorantagonist with ~15-30-fold preference for D3 over theD2 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 bothprolactinsecretion andstriataldopaminesynthesis, actions it does not share with the more selective (100-fold) D3 receptor antagonistsS-14,297 andGR-103,691.[4]
Inrodent studies, low doses of PNU-99,194 produceconditioned place preference (CPP) with no effect onintracranial self-stimulation (ICSS), whereas low doses of D3 agonists like7-OH-DPAT inhibit ICSS behavior and causeconditioned place aversion (CPA).[5][6][7] In contrast, high doses of PNU-99,194 produce CPA and inhibit ICSS, while high doses of 7-OH-DPAT result in the opposite.[5][6][7] Paralleling this, low doses of PNU-99,194 and 7-OH-DPAT inducehyperactivity andhypoactivity, respectively, whereas the inverse is seen at high doses with both agents.[2][3][7][8][9][10] These data indicate that the D3 receptor has biphasic effects onreward mechanisms andlocomotor activity, likely due to opposing roles ofautoreceptors versuspostsynapticreceptors.[8][11]
Other effects of PNU-99,194 at low doses in rodents include increasednociceptive responses,[12]hypothermia,[4][13]anxiolysis,[14] and facilitation oflearning andmemory,[12][15][16][17] as well as augmentation and inhibition, respectively, ofamphetamine-induced reward andbehavioral sensitization,[18][19] and reversal ofmorphine-induced CPP.[6] At high doses it inhibits theself-administration of cocaine in both rats and monkeys.[1][20]
