Pregnanolone
Endogenous neurosteroid and GABA-A positive allosteric modulator, also developed as the anesthetic eltanolone.
Pharmacology
Contents
WHAT IS PREGNANOLONE?
Detailed overview
Pregnanolone (eltanolone, 3alpha-hydroxy-5beta-pregnan-20-one) is an endogenous neurosteroid produced from progesterone by enzymatic conversion and closely related to allopregnanolone. Acting at a neurosteroid site on the GABA-A receptor, it works as a positive allosteric modulator that strengthens GABA's inhibitory effect, letting more chloride into neurons, lowering excitability and producing sedative, anti-anxiety and anticonvulsant effects. In the 1990s it was developed as the intravenous anesthetic eltanolone and tested in human clinical trials, but it was never marketed. Oral bioavailability is poor and it is rapidly metabolized, so it is not available as a practical supplement.
Mechanism
GABA-A positive allosteric modulator (neurosteroid)
Evidence
Human anesthesia trials (eltanolone)
Legal status
Not marketed (was a Phase III anesthetic)
Receptor profile
- GABA-A receptorsStrong
- Anxiety and stress modulationModerate
- NMDA receptors (in sulfated form)Weak
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Sedation and drowsiness
- Respiratory depression (slowed breathing) at anesthetic doses
- Changes in heart rate and blood pressure
- Involuntary movements, rarely convulsions at high doses
- Local injection-site reaction or pain (intravenous eltanolone lipid emulsion)
- Essentially inactive orally due to poor oral bioavailability
Contraindications · 4
- Pregnancy and breastfeeding: safety not established, avoid
- With other CNS depressants (alcohol, benzodiazepines, opioids): dangerous additive sedation and respiratory depression
- Respiratory insufficiency or severe hepatic disease
- Avoid driving and operating machinery due to the sedative effect
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Induction of anaesthesia with eltanolone at different rates of infusion in elderly patients
Myint Y, Peacock JE, Reilly CS
Eltanolone for induction of anaesthesia and to supplement nitrous oxide for minor gynaecological surgery
Rajah A, Powell H, Morgan M
Intravenous induction of general anaesthesia with eltanolone in children 6-15 years of age
Beskow A, Werner O, Westrin P
Hemodynamic effects during induction, laryngoscopy, and intubation with eltanolone or propofol
Sear JW, Jewkes C, Wanigasekera V
Acute neurosteroid modulation and subunit isolation of the GABA-A receptor in the bullfrog
Hollis DM, Goetz FW, Roberts SB, Boyd SK
3alpha5beta-Pregnanolone glutamate, a use-dependent NMDA antagonist, reversed spatial learning deficit
Vales K, Rambousek L, Holubova K, Svoboda J
FAQ
FAQ
Endogenous neurosteroid and GABA-A positive allosteric modulator, also developed as the anesthetic eltanolone.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.