OSU-6162

OSU-6162
(IUPAC) ime
(3S)-3-[3-(metilsulfonil)fenil]-1-propilpiperidin
Klinički podaci
Identifikatori
CAS broj 156907-84-5
ATC kod nije dodeljen
PubChem[1][2] 9795741
Hemijski podaci
Formula C15H23NO2S 
Mol. masa 281,413 g/mol
SMILES eMolekuli & PubHem
Farmakoinformacioni podaci
Trudnoća ?
Pravni status

OSU-6162 (PNU-96391) je jedinjenje koje deluje kao parcijalni agonist na dopaminskom D2 receptoru i na 5-HT2A receptoru. On deluje kao stabilizator dopamina na sličan način sa srodnim lekom pridopidinom, i ima antipsihotične, antiadiktivne i antiparkinsoniske efekte u životinjskim studijama.[3][4][5][6][7][8][9][10][11][12][13][14][15][16] Oba enantiomera pokazuju sličnu aktivnost ali imaju različite odnose efekata, pri čemu se (S) enantiomer (-)-OSU-6162 češće koristi u istraživanjima. On ima veći afinitet vezivanja za D2 ali je slabiji parcijalni agonist na 5-HT2A receptoru, dok (R) enantiomer (+)-OSU-6162 ima veću efikasnost na 5-HT2A i niži afinitet za D2 receptoru.[17][18]

Izvori

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  1. ↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519.  edit
  2. ↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1. 
  3. ↑ Ekesbo A, Andrén PE, Gunne LM, Tedroff J. (-)-OSU 6162 inhibits levodopa-induced dyskinesias in a monkey model of Parkinson's disease. Neuroreport. 1997 Jul 28;8(11):2567-70. PMID 9261828
  4. ↑ Tedroff J, Torstenson R, Hartvig P, Sonesson C, Waters N, Carlsson A, Neu H, Fasth KJ, Långström B. Effects of the substituted (S)-3-phenylpiperidine (-)-OSU6162 on PET measurements in subhuman primates: evidence for tone-dependent normalization of striatal dopaminergic activity. Synapse. 1998 Apr;28(4):280-7. PMID 9517836
  5. ↑ Tedroff J, Ekesbo A, Sonesson C, Waters N, Carlsson A. Long-lasting improvement following (-)-OSU6162 in a patient with Huntington's disease. Neurology. 1999 Oct 22;53(7):1605-6. PMID 10534281
  6. ↑ Nichols NF, Cimini MG, Haas JV, Staton BA, Tedroff J, Svensson KA. PNU-96391A (OSU6162) antagonizes the development of behavioral sensitization induced by dopamine agonists in a rat model for Parkinson's disease. Neuropharmacology. 2002 Oct;43(5):817-24. PMID 12384167
  7. ↑ Tamminga CA, Carlsson A. Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Current Drug Targets. CNS and Neurological Disorders. 2002 Apr;1(2):141-7. PMID 12769623
  8. ↑ Brandt-Christensen M, Andersen MB, Fink-Jensen A, Werge T, Gerlach J. The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys. Journal of Neural Transmission. 2006 Jan;113(1):11-9. PMID 15795789
  9. ↑ Rung JP, Carlsson A, Markinhuhta KR, Carlsson ML. The dopaminergic stabilizers (-)-OSU6162 and ACR16 reverse (+)-MK-801-induced social withdrawal in rats. Progress in Neuropsychopharmacology and Biological Psychiatry. 2005 Jun;29(5):833-9. PMID 15913873
  10. ↑ Natesan S, Svensson KA, Reckless GE, Nobrega JN, Barlow KB, Johansson AM, Kapur S. The dopamine stabilizers (S)-(-)-(3-methanesulfonyl-phenyl)-1-propyl-piperidine [(-)-OSU6162] and 4-(3-methanesulfonylphenyl)-1-propyl-piperidine (ACR16) show high in vivo D2 receptor occupancy, antipsychotic-like efficacy, and low potential for motor side effects in the rat. Journal of Pharmacology and Experimental Therapeutics. 2006 Aug;318(2):810-8. PMID 16648369
  11. ↑ Seeman P, Guan HC. Dopamine partial agonist action of (-)OSU6162 is consistent with dopamine hyperactivity in psychosis. European Journal of Pharmacology. 2007 Feb 28;557(2-3):151-3. PMID 17157291
  12. ↑ Lahti RA, Tamminga CA, Carlsson A. Stimulating and inhibitory effects of the dopamine "stabilizer" (-)-OSU6162 on dopamine D2 receptor function in vitro. Journal of Neural Transmission. 2007 Sep;114(9):1143-6. PMID 17612788
  13. ↑ Rung JP, Rung E, Helgeson L, Johansson AM, Svensson K, Carlsson A, Carlsson ML. Effects of (-)-OSU6162 and ACR16 on motor activity in rats, indicating a unique mechanism of dopaminergic stabilization. Journal of Neural Transmission. 2008 Jun;115(6):899-908. PMID 18351286
  14. ↑ Benaliouad F, Kapur S, Natesan S, Rompré PP. Effects of the dopamine stabilizer, OSU-6162, on brain stimulation reward and on quinpirole-induced changes in reward and locomotion. European Neuropsychopharmacology. 2009 Jun;19(6):416-30. PMID 19269794
  15. ↑ Dyhring T, Nielsen EØ, Sonesson C, Pettersson F, Karlsson J, Svensson P, Christophersen P, Waters N. The dopaminergic stabilizers pridopidine (ACR16) and (-)-OSU6162 display dopamine D(2) receptor antagonism and fast receptor dissociation properties. European Journal of Pharmacology. 2010 Feb 25;628(1-3):19-26. PMID 19919834
  16. ↑ Kara E, Lin H, Svensson K, Johansson AM, Strange PG. Analysis of the actions of the novel dopamine receptor-directed compounds (S)-OSU6162 and ACR16 at the D2 dopamine receptor. British Journal of Pharmacology. 2010 Nov;161(6):1343-50. DOI 10.1111/j.1476-5381.2010.01010.x. PMID 20804495
  17. ↑ Carlsson ML, Burstein ES, Kloberg A, Hansson S, Schedwin A, Nilsson M, Rung JP, Carlsson A. I. In vivo evidence for partial agonist effects of (-)-OSU6162 and (+)-OSU6162 on 5-HT2A serotonin receptors. Journal of Neural Transmission. 2011 Nov;118(11):1511-22. PMID 21874578
  18. ↑ Burstein ES, Carlsson ML, Owens M, Ma JN, Schiffer HH, Carlsson A, Hacksell U. II. In vitro evidence that (-)-OSU6162 and (+)-OSU6162 produce their behavioral effects through 5-HT2A serotonin and D2 dopamine receptors. Journal of Neural Transmission. 2011 Nov;118(11):1523-33. PMID 21866391

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