Tetrahydrodeoxycorticosterone
(Synonyms: Tetrahydro-11-deoxycorticosterone) 目录号 : GC63218
Tetrahydrodeoxycorticosterone 是一种神经类固醇，是一种有效的 GABAA 受体正变构调节剂 (PAM)。Tetrahydrodeoxycorticosterone 具有有效的神经抑制特性。
Cas No.:567-03-3
Sample solution is provided at 25 µL, 10mM.
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Tetrahydrodeoxycorticosterone, an neurosteroid, is a potent positive allosteric modulator (PAM) of GABAA receptor. Tetrahydrodeoxycorticosterone has potent neuroinhibitory properties[1][2].
The endogenous neurosteroid Tetrahydrodeoxycorticosterone (THDOC) at physiological concentrations selectively enhances tonic currents mediated by αβδ receptors[1].In hippocampus, 10 nM Tetrahydrodeoxycorticosterone reduces neuronal excitability by augmenting tonic αβδ receptor currents. In thalamocortical neurons, although 100 nM Tetrahydrodeoxycorticosterone enhances tonic currents, 10 nM Tetrahydrodeoxycorticosterone does not[1].
Concentrations of Tetrahydrodeoxycorticosterone (THDOC) in brain tissue from mice with hepatic encephalopathy (HE) resulting from toxic liver injury are sufficient to induce sedation in animals of the same species[2].
[1]. Hua-Jun Feng, et al. Comparison of αβδ and αβγ GABA A receptors: Allosteric modulation and identification of subunit arrangement by site-selective general anesthetics. Pharmacol Res. 2018 Jul;133:289-300.
[2]. Roger F Butterworth. Neurosteroids in hepatic encephalopathy: Novel insights and new therapeutic opportunities. J Steroid Biochem Mol Biol. 2016 Jun;160:94-7.
| Cas No. | 567-03-3 | SDF | |
| 别名 | Tetrahydro-11-deoxycorticosterone | ||
| 分子式 | C21H34O3 | 分子量 | 334.49 |
| 溶解度 | 储存条件 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9896 mL | 14.9481 mL | 29.8963 mL |
| 5 mM | 0.5979 mL | 2.9896 mL | 5.9793 mL |
| 10 mM | 0.299 mL | 1.4948 mL | 2.9896 mL |
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Mirtazapine does not influence Tetrahydrodeoxycorticosterone levels in depressed patients
World J Biol Psychiatry 2010 Mar;11(2 Pt 2):308-13.PMID:20218794DOI:10.3109/15622970701639429.
Background: Among the neuroactive steroids, 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA) system. The antidepressant mirtazapine has been shown to attenuate HPA axis activity and to increase the concentrations of 3alpha-reduced metabolites of progesterone in depressed patients. In the present study, the impact of mirtazapine on 3alpha,5alpha-THDOC levels was investigated in relation to clinical response in depressed patients. Method: A total of 23 drug-free inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 08:00 h and were quantified for 3alpha,5alpha-THDOC levels. Results: 3alpha,5alpha-THDOC levels were not correlated with demographic and clinical parameters such as age and severity of depression. Moreover, 5-week treatment with mirtazapine did not influence the 3alpha,5alpha-THDOC in the depressed patients, neither in responders nor in non-responders. Conclusion: Putative increasing effects of mirtazapine on 3alpha-reduced neuroactive steroids such as 3alpha,5alpha-THDOC which may be mediated via an impact on the neurosteroidogenic enzyme 3alpha-hydroxysteroid dehydrogenase seem to be counterbalanced by the mirtazapine-induced inhibition of ACTH secretion which directly influences the 3alpha,5alpha-THDOC release of the adrenal cortex.
Antinociceptive activity of a neurosteroid Tetrahydrodeoxycorticosterone (5alpha-pregnan-3alpha-21-diol-20-one) and its possible mechanism(s) of action
Indian J Exp Biol 2001 Dec;39(12):1299-301.PMID:12018528doi
The present study investigates the effects of a neurosteroid Tetrahydrodeoxycorticosterone (5alpha-pregnan-3alpha-21-diol-20-one) in two experimental models of pain sensitivity in mice. Tetrahydrodeoxycorticosterone (2.5, 5 mg/kg, i.p.) dose dependently decreased the licking response in formalin test and increased the tail flick latency (TFL) in tail flick test. Bicuculline (2 mg/kg, i.p.), a GABA(A) receptor antagonist blocked the antinociceptive effect of Tetrahydrodeoxycorticosterone in TFL test but failed to modulate licking response in formalin test. Naloxone (1 mg/kg, i.p.), an opioid antagonist effectively attenuated the analgesic effect of Tetrahydrodeoxycorticosterone in both the models. Tetrahydrodeoxycorticosterone pretreatment potentiated the antinociceptive response of morphine, an opioid compound and nimodipine, a calcium channel blocker in formalin as well as TFL test. Thus, Tetrahydrodeoxycorticosterone exerts an analgesic effect, which may be mediated by modulating GABA-ergic and/or opioid-ergic mechanisms and voltage-gated calcium channels.
Actions of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone on single neurones of the mesencephalic reticular formation in the rat
Neurosci Lett 1989 Sep 25;104(1-2):115-20.PMID:2812524DOI:10.1016/0304-3940(89)90339-x.
The effects of microinjections of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (3 alpha-THDOC) on single neurones of the mesencephalic reticular formation (MRF) were investigated in rats anaesthetized with urethan. Microinjections of approximately 100 nl of 0.5-2 microM 3 alpha-THDOC inhibited firing of 105 of 112 neurones (94%). Microinjections of approximately 100 nl of 100-250 nM of 3 alpha-THDOC did not alter neuronal activity, but in 52 of 68 cases (76%) it potentiated the inhibitory action of microiontophoretically applied gamma-aminobutyric acid (GABA). The 3 beta-isomer of Tetrahydrodeoxycorticosterone did not elicit any changes in neuronal firing. The effects of 3 alpha-THDOC were reversibly antagonized by microiontophoretically applied bicuculline. This 'in vivo' study supports the hypothesis that 3 alpha-THDOC may function as endogenous modulator of GABAA-mediated inhibition in various physiopathological conditions.
Neonatal treatment of rats with the neuroactive steroid Tetrahydrodeoxycorticosterone (THDOC) abolishes the behavioral and neuroendocrine consequences of adverse early life events
J Clin Invest 1997 Mar 1;99(5):962-6.PMID:9062354DOI:10.1172/JCI119261.
Stressful experience during early brain development has been shown to produce profound alterations in several mechanisms of adaptation, while several signs of behavioral and neuroendocrine impairment resulting from neonatal exposure to stress resemble symptoms of dysregulation associated with major depression. This study demonstrates that when applied concomitantly with the stressful challenge, the steroid GABA(A) receptor agonist 3,21-dihydropregnan-20-one (Tetrahydrodeoxycorticosterone, THDOC) can attenuate the behavioral and neuroendocrine consequences of repeated maternal separation during early life, e.g., increased anxiety, an exaggerated adrenocortical secretory response to stress, impaired responsiveness to glucocorticoid feedback, and altered transcription of the genes encoding corticotropin-releasing hormone (CRH) in the hypothalamus and glucocorticoid receptors in the hippocampus. These data indicate that neuroactive steroid derivatives with GABA-agonistic properties may exert persisting stress-protective effects in the developing brain, and may form the basis for therapeutic agents which have the potential to prevent mental disorders resulting from adverse experience during neonatal life.
Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha Tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers
Neuropsychopharmacology 2005 Jan;30(1):192-5.PMID:15467707DOI:10.1038/sj.npp.1300572.
3alpha-reduced neuroactive steroids such as 3alpha, 5alpha-tetrahydroprogesterone (3alpha, 5alpha-THP) and 3alpha, 5alpha-tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3alpha, 5alpha-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3alpha, 5alpha-THDOC concentrations during experimental panic induction. Therefore, we quantified 3alpha, 5alpha-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3alpha, 5alpha-THDOC, ACTH and cortisol concentrations. This increase in 3alpha, 5alpha-THDOC might be a consequence of hypothalamic-pituitary-adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.