R015-4513

Ro15-4513 (IUPAC: Ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,4-benzodiazepine-3-carboxylate) is a weak partial inverse agonist of the benzodiazepine class of drugs, developed by Hoffmann–La Roche in the 1980s. It acts as an inverse agonist, which is similar in action to a competitive antagonist, and can therefore serve as an antidote to the acute impairment caused by alcohols, including ethanol, isopropanol, tert-butyl alcohol, tert-amyl alcohol, 3-methyl-3-pentanol, methylpentynol, and ethchlorvynol. Ro15-4513 is structurally related to the benzodiazepine antidote flumazenil.

Mechanism of Action

Ro15-4513 functions as a weak partial inverse agonist at the [[GABA_A receptor]], which is a different mechanism of action compared to most benzodiazepines that act as full agonists at this receptor. By acting as an inverse agonist, Ro15-4513 reduces the effect of GABA, the primary inhibitory neurotransmitter in the brain, leading to a decrease in the depressant effects of alcohols on the central nervous system.

Clinical Uses

While Ro15-4513 has been studied primarily for its potential to counteract the effects of alcohol intoxication, its clinical use is limited due to its weak partial agonist activity, which makes it less effective than other available treatments like flumazenil. However, its unique action on the GABA_A receptor and its ability to counteract the effects of various alcohols make it a compound of interest for research into treatments for acute alcohol intoxication and possibly for other conditions influenced by GABAergic activity.

Adverse Effects

As with other benzodiazepines and benzodiazepine-like substances, potential adverse effects of Ro15-4513 may include drowsiness, confusion, and impaired motor function. However, due to its status as a weak partial inverse agonist, these effects may be less pronounced compared to full agonists of the benzodiazepine class.

Research

Research on Ro15-4513 has contributed to a better understanding of the GABA_A receptor and the complex actions of benzodiazepines and their analogs. Studies involving Ro15-4513 have also helped elucidate the role of specific subunits of the GABA_A receptor in the effects of alcohol and benzodiazepines, potentially guiding the development of more targeted therapies in the future.

See Also

• Benzodiazepine
• Flumazenil
• [[GABA_A receptor]]
• Inverse agonist
• Alcohol intoxication