A neurosteroid and positive allosteric modulator of GABAA receptors
THDOC is a neurosteroid and positive allosteric modulator of GABAA receptors.1 It inhibits binding of the convulsant t-butylbicyclophosphorothionate (TBPS) and increases binding of the benzodiazepine flunitrazepam to rat synaptosomal membrane preparations in a concentration-dependent manner.2 THDOC potentiates GABA-induced chloride currents in cultured rat hippocampal and spinal cord neurons. It inhibits seizures induced by pilocarpine or pentylenetetrazol in mice (ED50s = 7.3 and 15 mg/kg, respectively).3 THDOC (20 mg/kg) increases the number of entries into and percentage of time spent in the open arms of the elevated plus maze in mice, indicating anxiolytic activity.4
|1. Usami, N., Yamamoto, T., Shintani, S., et al. Substrate specificity of human 3(20)α-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol. Pharm. Bull. 25(4), 441-445 (2002).|2. Majewska, M.D., Harrison, N.L., Schwartz, R.D., et al. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232(4753), 1004-1007 (1986).|3. Kokate, T.G., Cohen, A.L., Karp, E., et al. Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice. Neuropharmacology 35(8), 1049-1056 (1996).|4. Rodgers, R.J., and Johnson, N.J. Behaviorally selective effects of neuroactive steroids on plus-maze anxiety in mice. Pharmacol. Biochem. Behav. 59(1), 221-232 (1998).
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