Clavulanic acid: a competitive inhibitor of beta-lactamases with novel anxiolytic-like activity and minimal side effects
Department of Psychiatry
Medical Subject Headings
Animals; *Anti-Anxiety Agents; Chlordiazepoxide; Clavulanic Acid; Cricetinae; Enzyme Inhibitors; Learning; Male; Maze Learning; Memory; Mesocricetus; Motor Activity; Neurosecretory Systems; Penile Erection; Rats; Rats, Wistar; Saguinus; Stress, Psychological; beta-Lactamases
Clavulanic acid is a member of the beta lactam family of antibiotics with little or no intrinsic antibacterial activity of its own; instead, it is used to enhance the activity of antibiotics by blocking bacterial beta-lactamases. Because clavulanic acid by itself is very safe, orally active and shows good brain penetrance, we sought to determine if it had any potential as a psychotherapeutic. Clavulanic acid was a tested across three mammalian species, hamsters, rats and cotton-top tamarin monkeys in a series of behavioral assays designed to screen for anxiolytic activity. In addition, several studies were done in rodents to compare the behavioral profile of clavulanic acid to the commonly prescribed benzodiazepines, particularly with respect to their unwanted side effects of motor depression, amnesia and neuroendocrine dysregulation. Our findings show that clavulanic acid is a highly potent anxiolytic in rodents without altering motor activity in the open field test, normal learning and memory in the Morris water maze, or normal stress hormone release. Orally administered clavulanic acid significantly reduces measures of anxiety in male/female pairs of cotton-top tamarins. In addition, male tamarins showed a highly significant increase in sexual arousal as measured by the number of penile erections. The fact clavulanic acid has anxiolytic activity in the tamarin holds the promise that this drug may be an effective therapeutic for the treatment of anxiety disorders in humans.
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Citation: Pharmacol Biochem Behav. 2009 Aug;93(2):112-20. Epub 2009 Apr 24. Link to article on publisher's site