 | |
| Clinical data | |
|---|---|
| Other names | GSK598809 |
| Drug class | Dopamine D3 receptor antagonist |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C22H23F4N5OS |
| Molar mass | 481.51 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
GSK-598809 is a selective dopamine D3 receptor antagonist that is or was under development for the treatment of substance-related disorders, smoking withdrawal, and eating disorders like binge eating disorder. [1] [2] [3] [4]
The drug is highly selective for the dopamine D3 receptor (Ki = 6.2 nM) over the dopamine D2 receptor (Ki = 740 nM) (~120-fold preference for the D3 receptor over the D2 receptor). [3] A single dose of GSK-598809 achieved 72 to 89% occupancy of the D3 receptor in smokers. [3]
Side effects of GSK-598809 in clinical trials have included headache and somnolence with no sedation or extrapyramidal symptoms. [2] This is in contrast to dopamine D2 receptor antagonists, which are associated with sedation, motor side effects, reduced activity, and emotional blunting. [2] However, GSK-598809 has been associated with cardiovascular side effects at high doses. [2] It increases blood pressure in animals and this effect was especially strong in the presence of cocaine, which dampened enthusiasm for its clinical development for cocaine use disorder. [3] However, other more recently developed and selective D3 receptor antagonists like (R)-VK4-116 and (R)-VK4-40 do not share these cardiovascular side effects. [3]
GSK-598809 was first described in the scientific literature by 2009. [5] [6] As of August 2023, no recent development of GSK-598809 has been reported for substance-related disorders, smoking withdrawal, or eating disorders since July 2016. [1] GSK-598809 reached at least phase 1 clinical trials. [1] [2] According to a 2021 review, the clinical effects of GSK-598809 and other experimental dopamine D3 receptor antagonists were mixed or unsatisfactory and thus their development was discontinued early into clinical trials. [4] In any case, signs of clinical efficacy were reported to have been observed. [3] [2] [4]