PNU-99,194

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PNU-99,194
File:PNU-99194A-structure.png
Systematic (IUPAC) name
5,6-dimethoxy-N,N-dipropyl-2,3-dihydro-1H-inden-2-amine
Clinical data
Routes of
administration		 Oral
Legal status
Legal status
  • Uncontrolled
Identifiers
CAS Number 82668-33-5
83598-46-3 (Maleate)
153570-58​-2 (Hydrochloride)
ATC code none
PubChem CID 5626
ChemSpider 5424
Chemical data
Formula C17H27NO2
Molar mass 277.40 g/mol[[Script error: No such module "String".]]
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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).[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 induce hyperactivity and hypoactivity, respectively, whereas the inverse is seen at high doses with both agents.[8][9][3][2][7][10] These data indicate that the D3 receptor has biphasic effects on reward mechanisms and locomotor activity, likely due to opposing roles of autoreceptors versus postsynaptic receptors.[11][8]

Other effects of PNU-99,194 at low doses in rodents include increased nociceptive responses,[12] hypothermia,[13][4] anxiolysis,[14] and facilitation of learning and memory,[15][16][12][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.[20][1]

See also

References

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  1. ↑ 1.0 1.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  2. ↑ 2.0 2.1 Waters N, Svensson K, Haadsma-Svensson SR, Smith MW, Carlsson A (1993). "The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotor activity". Journal of Neural Transmission. General Section. 94 (1): 11–9. PMID 8129881. 
  3. ↑ 3.0 3.1 Kling-Petersen T, Ljung E, Svensson K (1995). "Effects on locomotor activity after local application of D3 preferring compounds in discrete areas of the rat brain". Journal of Neural Transmission. General Section. 102 (3): 209–20. PMID 8788069. 
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  5. ↑ 5.0 5.1 Kling-Petersen T, Ljung E, Wollter L, Svensson K (1995). "Effects of dopamine D3 preferring compounds on conditioned place preference and intracranial self-stimulation in the rat". Journal of Neural Transmission. General Section. 101 (1-3): 27–39. PMID 8695055. 
  6. ↑ 6.0 6.1 6.2 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  7. ↑ 7.0 7.1 7.2 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  8. ↑ 8.0 8.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  9. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  10. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  11. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  12. ↑ 12.0 12.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  13. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Rogóz Z, Kłodzińska A, Maj J (2000). "Anxiolytic-like effect of nafadotride and PNU 99194A, dopamine D3 receptor antagonists in animal models". Polish Journal of Pharmacology. 52 (6): 459–62. PMID 11334239. 
  15. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  16. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  17. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  18. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  19. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  20. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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