Allopregnanolone Analysis

Designing a Therapeutic Dosing Regimen for a Novel Potential Treatment of Alzheimer’s Disease

Allopregnanolone is a metabolite of progesterone and a naturally occurring steroid hormone, which acts as a positive allosteric modulator on the GABAA receptor, producing anaesthetic, anxiolytic and sedative effects. The notable exception to this appears to be in the brains of adolescents, where it acts as a GABAA antagonist, causing mood swings. (National Center for Biotechnology Information, n.d.)

It is found to be secreted in the urine of pregnant women (National Center for Biotechnology Information, n.d.), and levels have been found to naturally fluctuate during pregnancy, the menstrual cycle (Luisi S, 2000), and stress (Girdler SS, 2001).

The chemical properties of allopregnanolone make it easy for the molecules to pass from the

Ototopical formulation is painless, easy to use, and carries a low risk of infection. It is, however, somewhat time-consuming, as it requires that the patient remain supine for up to 5 minutes. First pass metabolism could be avoided, and allopregnanolone does not appear to be ototoxic. Bioavailability is likely to be high, although no specific data has yet been collected for ototopical administration of allopregnanolone.

A potential pitfall of the ototopical route of administration could be cerumen. Cerumen is very lipophilic, meaning that if the allopregnanolone were applied onto the cerumen it would likely become trapped, thus reducing the bioavailability and increasing the half-life, but ototopical application could potentially be extended past the cerumen into the otic canal. Alternatively, the quantity of cerumen could be reduced, either by solubilisation or removal, prior to ototopical administration of