ABT-354
Experimental 5-HT6 receptor antagonist for cognitive disorders
From Wikipedia, the free encyclopedia
ABT-354 (also known as SLV-354 or SLV354) is an investigational small molecule drug developed by AbbVie, Inc. as a selective antagonist of the serotonin 5-HT6 receptor (HTR6), with intended applications in the treatment of cognitive disorders such as mild-to-moderate Alzheimer’s disease.[1]
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| Other names | SLV-354, SLV354 |
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| Formula | C20H25N5O3S2 |
| Molar mass | 447.57 g·mol−1 |
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Mechanism of action
ABT-354 selectively antagonizes the 5-HT6 receptor, a G protein-coupled receptor almost exclusively expressed in the central nervous system (CNS), where it modulates neurotransmitter systems including acetylcholine, glutamate, dopamine, and norepinephrine.[2] Blockade of 5-HT6 receptors has been shown in preclinical models to enhance cholinergic and glutamatergic neurotransmission, leading to improvements in cognitive performance and memory.[2][3] Evidence from animal studies indicates that both 5-HT6 receptor antagonists and agonists can paradoxically exert procognitive, antidepressant, and anxiolytic effects, demonstrates the complex pharmacology of this receptor class.[2][3]
Other 5-HT6 antagonists
Despite promising preclinical results, several selective 5-HT6 receptor antagonists (e.g., idalopirdine, intepirdine) have failed to demonstrate significant cognitive benefits in late-stage clinical trials for Alzheimer’s disease, possibly due to the complexity of the disorder and the need for multitarget approaches.[3] Recent advances in drug design, such as the development of neutral antagonists and multitarget ligands, may offer new opportunities for therapeutic intervention.[4][5]
Clinical trials
Clinical trials for ABT-354 have focused on assessing its safety, tolerability, and pharmacokinetics in patients with mild-to-moderate Alzheimer’s disease who are concurrently receiving stable doses of acetylcholinesterase inhibitors.[6] These studies included participants aged 55 to 90 years and employed multiple dosing regimens.[6]