OSU-6162 (PNU-96391) is a compound which acts as a partial agonist at both dopamine D2 receptors and 5-HT2A 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-HT2A, while the (R) enantiomer (+)-OSU-6162 has higher efficacy at 5-HT2A but lower D2 affinity.[15][16]
Quick Facts Clinical data, ATC code ...
OSU-6162![Thumb](//upload.wikimedia.org/wikipedia/commons/thumb/8/8e/OSU-6162.svg/220px-OSU-6162.svg.png) |
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ATC code | |
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(3S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine
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ECHA InfoCard | 100.216.320 ![Edit this at Wikidata](//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/10px-OOjs_UI_icon_edit-ltr-progressive.svg.png) |
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Formula | C15H23NO2S |
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Molar mass | 281.41 g·mol−1 |
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3D model (JSmol) | |
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CCCN1CCC[C@H](C1)C2=CC(=CC=C2)S(=O)(=O)C
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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
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Tedroff J, Ekesbo A, Sonesson C, Waters N, Carlsson A (October 1999). "Long-lasting improvement following (-)-OSU6162 in a patient with Huntington's disease". Neurology. 53 (7): 1605–6. doi:10.1212/wnl.53.7.1605. PMID 10534281.
Nichols NF, Cimini MG, Haas JV, Staton BA, Tedroff J, Svensson KA (October 2002). "PNU-96391A (OSU6162) antagonizes the development of behavioral sensitization induced by dopamine agonists in a rat model for Parkinson's disease". Neuropharmacology. 43 (5): 817–24. doi:10.1016/s0028-3908(02)00144-2. PMID 12384167. S2CID 22101873.
Tamminga CA, Carlsson A (April 2002). "Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis". Current Drug Targets. CNS and Neurological Disorders. 1 (2): 141–7. doi:10.2174/1568007024606195. PMID 12769623.
Brandt-Christensen M, Andersen MB, Fink-Jensen A, Werge T, Gerlach J (January 2006). "The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys". Journal of Neural Transmission. 113 (1): 11–9. doi:10.1007/s00702-005-0297-1. PMID 15795789. S2CID 21099503.
Rung JP, Carlsson A, Markinhuhta KR, Carlsson ML (June 2005). "The dopaminergic stabilizers (-)-OSU6162 and ACR16 reverse (+)-MK-801-induced social withdrawal in rats". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 29 (5): 833–9. doi:10.1016/j.pnpbp.2005.03.003. PMID 15913873. S2CID 20868201.
Natesan S, Svensson KA, Reckless GE, Nobrega JN, Barlow KB, Johansson AM, Kapur S (August 2006). "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". The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 810–8. doi:10.1124/jpet.106.102905. PMID 16648369. S2CID 9385308.
Seeman P, Guan HC (February 2007). "Dopamine partial agonist action of (-)OSU6162 is consistent with dopamine hyperactivity in psychosis". European Journal of Pharmacology. 557 (2–3): 151–3. doi:10.1016/j.ejphar.2006.11.016. PMID 17157291.
Lahti RA, Tamminga CA, Carlsson A (September 2007). "Stimulating and inhibitory effects of the dopamine "stabilizer" (-)-OSU6162 on dopamine D2 receptor function in vitro". Journal of Neural Transmission. 114 (9): 1143–6. doi:10.1007/s00702-007-0784-7. PMID 17612788. S2CID 23496944.
Rung JP, Rung E, Helgeson L, Johansson AM, Svensson K, Carlsson A, Carlsson ML (June 2008). "Effects of (-)-OSU6162 and ACR16 on motor activity in rats, indicating a unique mechanism of dopaminergic stabilization". Journal of Neural Transmission. 115 (6): 899–908. doi:10.1007/s00702-008-0038-3. PMID 18351286. S2CID 20687327.
Benaliouad F, Kapur S, Natesan S, Rompré PP (June 2009). "Effects of the dopamine stabilizer, OSU-6162, on brain stimulation reward and on quinpirole-induced changes in reward and locomotion". European Neuropsychopharmacology. 19 (6): 416–30. doi:10.1016/j.euroneuro.2009.01.014. PMID 19269794. S2CID 19419177.
Carlsson ML, Burstein ES, Kloberg A, Hansson S, Schedwin A, Nilsson M, et al. (November 2011). "I. In vivo evidence for partial agonist effects of (-)-OSU6162 and (+)-OSU6162 on 5-HT2A serotonin receptors". Journal of Neural Transmission. 118 (11): 1511–22. doi:10.1007/s00702-011-0704-8. PMID 21874578. S2CID 43580367.
Burstein ES, Carlsson ML, Owens M, Ma JN, Schiffer HH, Carlsson A, Hacksell U (November 2011). "II. In vitro evidence that (-)-OSU6162 and (+)-OSU6162 produce their behavioral effects through 5-HT2A serotonin and D2 dopamine receptors". Journal of Neural Transmission. 118 (11): 1523–33. doi:10.1007/s00702-011-0701-y. PMID 21866391. S2CID 763630.