Doxylamine

Doxylamine is a first-generation antihistamine and acts as a histamine H1 receptor antagonist. Doxylamine is orally active, possessing analgesic and hypnotic activities. Doxylamine enhances the activities of CYP2B, CYP2A, CYP3A and thyroxine-glucuronosyltransferase via promoting substrate hydroxylation and thyroxine metabolic pathways. Doxylamine decreases serum thyroxine (T4) level and elevates serum thyroid-stimulating hormone (TSH) level. Doxylamine induces liver enlargement and increases the activities of hepatic microsomal cytochrome P450, cytochrome b5 and NADPH-cytochrome c reductase. Doxylamine can be used for the research of nausea, allergy, insomnia^[1][2][3]. In Vivo:Doxylamine (administered daily via diet for 7 or 15 days at doses of 40-1500 ppm) acts as a phenobarbital-type inducer of hepatic microsomal cytochrome P450 in B6C3F1 mice, with a maximum 38-fold induction of CYP2B activity; at the highest dose, it also alters thyroid hormone homeostasis by decreasing serum T₄ and increasing serum TSH^[1].
Doxylamine (1-2 mg; 4% solution (25 μL); oral administration; intravenous injection; intranasal administration; single dose) shows a bioavailability of 70.8% via intranasal delivery in male Sprague-Dawley rats, with rapid absorption and no nasal epithelial damage^[3].