Tetrahydrodeoxycorticosterone

Tetrahydrodeoxycorticosterone (THDOC) is a neurosteroid that has potent GABAergic effects. It is synthesized from progesterone in the adrenal gland and the central nervous system, particularly in the hippocampus and amygdala.

Synthesis

The synthesis of THDOC involves several enzymatic reactions. Progesterone is first converted to dihydroprogesterone by the enzyme 5α-reductase, and then to allopregnanolone by the enzyme 3α-hydroxysteroid dehydrogenase. Allopregnanolone is then converted to THDOC by the enzyme 21-hydroxylase.

Function

THDOC is a potent positive allosteric modulator of the GABA_A receptor, the major inhibitory neurotransmitter receptor in the brain. It enhances the effects of GABA at this receptor, leading to increased inhibitory effects on neuronal activity. This results in sedative, anxiolytic, and anticonvulsant effects.

Clinical significance

Due to its potent GABAergic effects, THDOC has been investigated for potential therapeutic uses in conditions such as anxiety disorders, epilepsy, and insomnia. However, its use is limited by its sedative effects and potential for dependence and withdrawal symptoms.

See also

• Neurosteroid
• GABA_A receptor
• Progesterone
• 5α-reductase
• 3α-hydroxysteroid dehydrogenase
• 21-hydroxylase
• Anxiety disorders
• Epilepsy
• Insomnia