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| Clinical data | |
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| Other names | S-32504; S-32,504 |
| Routes of administration | Unspecified[1] |
| Drug class | Dopamine receptor agonist;DopamineD2 andD3 receptoragonist |
| ATC code |
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| Identifiers | |
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| PubChemCID | |
| ChemSpider | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C16H22N2O2 |
| Molar mass | 274.364 g·mol−1 |
| 3D model (JSmol) | |
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S32504 is adopamineD2 andD3 receptoragonist which was under development for the treatment ofParkinson's disease but was never marketed.[1][2][3] Itsroute of administration was unspecified.[1]
S32504 acts as apotent andselectiveagonist of thedopamineD3 andD2 receptors, withEC50Tooltip half-maximal effective concentration values of 2.0–3.2 nM and 2.5–398 nM, respectively, depending on theassay.[3] It is a preferential agonist of the dopamine D3 receptor over the dopamine D2 receptor.[3] The drug showed littleaffinity for or activity at more than 50 otherreceptors andtargets, including the dopamineD1,D4, andD5 receptors and theserotonin5-HT1A and5-HT2A receptors, among others.[3] S32504 suppressed the activity ofdopaminergicneurons in theventral tegmental area (VTA) in rodents.[3] In addition, it potently reduced levels of dopamine in thestriatum,nucleus accumbens, andfrontal cortex, which could be reversed by the dopamine D2 and D3 receptor antagonisthaloperidol and by the selective dopamine D2 receptor antagonistL-741,626, but not by the selective dopamine D3 receptor antagonistS33084.[3]
The drug producesantiparkinsonian effects in rodents and monkeys andantidepressant- andanxiolytic-like effects in rodents.[4][5] The antiparkinsonian effects of S32504 could be blocked by the dopamine D2 and D3 receptor antagonists haloperidol andraclopride and by L-741,626, but not by S33084, suggesting mediation of these actions by the dopamine D2 receptor and not by the dopamine D3 receptor.[4] However, the dopamine D3 receptor appeared to be involved in dopaminergicneuroprotective effects of S32504.[4] The antidepressant- and anxiolytic-like effects of S32504 were blocked by haloperidol, raclopride, and L-741,626 but not by S33084, again suggesting involvement of the dopamine D2 receptor and not the dopamine D3 receptor in these effects.[5] In rats treated with thedopamine depleting agentreserpine and monkeys treated with thedopaminergic neurotoxinMPTP, S32504 reversedhypolocomotion.[4] Conversely, in untreated rodents, S32504 producedhypolocomotion over a wide range of doses and did not producehyperlocomotion at any assessed dose.[5]
Analogues of S32504 with enhanced affinity and selectivity for the dopamine D3 receptor over the dopamine D2 receptor have been developed and described.[6]
S32504 was first described in thescientific literature by 1999.[7][8]
S32504 was being developed for the treatment ofParkinson's disease byServier inFrance.[1][2] It reached thepreclinical research stage of development prior to its development being discontinued.[1][2] No recent development was reported by 2003.[1]