Baclofen: Therapeutic and toxic mechanisms of action (review)

Baclofen is a muscle relaxant, which is a beta-p-chlorophenyl derivative of an inhibitory neuro transmitter GABA. This drug may have serious side effects and cause life-threatening conditions which may result from an unintentional overdose of the drug prescribed by a doctor, idiosyncrasy, suicidal behavior or criminal acts. The aim of the review is to examine the mechanisms of therapeutic and toxic effects of baclofen, its effects on cellular receptors to clarify the pathogenesis of life-threatening conditions caused by poisoning with this drug. The search was done using the PubMed and Scopus databases, and the final selection of 82 sources was made based on the relevance to the topic of this review and the type of article. The review included both the results of randomized studies and individual reports. The review briefly discusses the history of baclofen synthesis and its application in clinical practice, indications for prescription, mechanism of action and the specific features of its metabolism, its effect on the CNS, signs and symptoms of withdrawal syndrome, overdose and acute poisoning, as well as the interaction of baclofen with other drugs. Conclusion. Multiple studies failed to make definite conclusions about mechanisms of baclofen toxicity. To completely reveal the pathogenesis of life-threatening conditions occurring due to baclofen use, further studies of molecular and cellular effects of this drug, as well as genetic factors controlling its metabolism, are warranted. © 2020, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.