3-beta,5-alpha-Tetrahydrodeosoxycorticosterone

Description

3β,5α-THDOC is a neurosteroid. It inhibits seizures induced by pilocarpine, but not pentylenetetrazol (PTZ; ), in mice (ED₅₀s = 45.9 and >100 mg/kg, respectively). 3β,5α-THDOC has been found in the urine of women during the third trimester of pregnancy.

Uses

3β,5α-Tetrahydrodeoxycorticosterone is a novel derivative of the steroid Dehydroepiandrosterone (DHEA), a known uncompetitive inhibitor of Glucose 6-Phosphate Dehydrogenase (G6PD). Studies have shown that 3β,5α-Tetrahydrodeoxycorticosterone may have potential function in the modulation of calcium and GABAA-gated chloride channel currents found in rat and guinea-pig neurons.

in vitro

epiallopregnanolone showed no effects on the gaba-mediated chloride flux through several types of recombinant gaba receptors. epiallopregnanolone inhibited the allopregnanolone-stimulated gaba-mediated chloride flux through gabaa receptors. epiallopregnanolone antagonized the inhibitory effects of allopregnanolone and ethanol on the population spike in the ca1 region of the hippocampal brain slices [1]. epiallopregnanolone selectively blocked the allopregnanolone inhibition of the population spike in the rat hippocampal ca1[3].

in vivo

in rats trained to discriminate either 0.8g/kg or 1.2 g/kg ethanol, 100 mg/kg epiallopregnanolone treatment decreased the maximum effect by 40% and 54% ethanol lever, respectively. epiallopregnanolone significantly decreased response rates when compared with control condition [1].

References

[1] ginsburg b c, lamb r j. alphaxalone and epiallopregnanolone in rats trained to discriminate ethanol[j]. alcoholism: clinical and experimental research, 2005, 29(9): 1621-1629.
[2] macdonald r l, olsen r w. gabaa receptor channels[j]. annual review of neuroscience, 1994, 17(1): 569-602.
[3] wang m, bckstrm t, landgren s. epiallopregnanolone selectively blocks the allopregnanolone inhibition of the population spike in the rat hippocampal ca1[j]. acta physiologica scandinavica, 1999, 167(2): a5-a5.