OSU-6162

OSU-6162

Systematic (IUPAC) name
(3S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine
Identifiers
CAS Number	156907-84-5
ATC code	none
PubChem	CID 9795741
ChemSpider	7971507
ChEMBL	CHEMBL311730
Chemical data
Formula	C15H23NO2S
Molar mass	281.413 g/mol
SMILES CCCN1CCC[C@H](C1)C2=CC(=CC=C2)S(=O)(=O)C
InChI InChI=1S/C15H23NO2S/c1-3-9-16-10-5-7-14(12-16)13-6-4-8-15(11-13)19(2,17)18/h4,6,8,11,14H,3,5,7,9-10,12H2,1-2H3/t14-/m1/s1 Key:GZVBVBMMNFIXGE-CQSZACIVSA-N

OSU-6162 (PNU-96391) is a compound which acts as a partial agonist at both dopamine D₂ receptors and 5-HT_2A receptors. It acts as a dopamine stabilizer in a similar manner to the closely related drug pridopidine, and has antipsychotic, anti-addictive and anti-Parkinsonian effects in animal studies.^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14]} Both enantiomers show similar activity but with different ratios of effects, with the (S) enantiomer (–)-OSU-6162 that is more commonly used in research, having higher binding affinity to D₂ but is a weaker partial agonist at 5-HT_2A, while the (R) enantiomer (+)-OSU-6162 has higher efficacy at 5-HT_2A but lower D₂ affinity.^[15][16]

See also

• PF-219,061

References

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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