Arbaclofen

Synonyms :
(R)-4-Amino-3-(4-chlorophenyl)butan­oic acid, (R)-Baclofen, OS440, STX209

Status : investigational

Description

Arbaclofen, or STX209, is the R-enantiomer of baclofen. It is believed to be a selective gamma-amino butyric acid type B receptor agonist, and has been investigated as a treatment for autism spectrum disorder and fragile X syndrome in randomized, double blind, placebo controlled trials. It has also been investigated as a treatment for spasticity due to multiple sclerosis and spinal cord injury. Arbaclofen was investigated as a treatment for gastroesophageal reflux disease (GERD); however, with disappointing results.

Used

Investigated in clinical trials as a potential treatment for spasticity in multiple sclerosis, autism spectrum disorder, and social withdrawal in fragile X syndrome.

Mechanism Of Action

Arbaclofen, or R-baclofen, acts upstream of the mGluR5 receptor to increase inhibitory neurotransmission. It is the isomer of baclofen which harbors antispastic activity.

Absorption

Unlike baclofen, absorption of arbaclofen is not limited to the upper small intestine. Arbaclofen can also be absorbed in the lower small intestine and the colon, allowing for the development of sustained release formulations.

Elimination Route

>80% of R-baclofen is renally eliminated unchanged.

Clearance

Blood clearance of an IV bolus of R-baclofen in rats, monkeys, and dogs, resulted in a half life of 1.6-3.4hours, in one study. Total blood clearance was reported to be 0.51±0.13L/h/kg in rats, 0.31±0.11L/h/kg in monkeys, and 0.24±0.01L/h/kg in dogs. (2)

Chemical Classification

Chemical Name

(R)-4-Amino-3-(4-chlorophenyl)butan­oic acid

Calculated Property

kind Value Source

Target within organism

  • Gamma-aminobutyric acid type B receptor subunit 1 : in Human
  • Gamma-aminobutyric acid type B receptor subunit 2 : in Human