Doxepin

Doxepin is an orally active, blood-brain barrier penetrant tricyclic antidepressant with multiple activities including hypnosis, sedation, analgesia and vasodilation. Doxepin enhances the expression of PSD-95 and synapsin 1 via the PI3K/AKT/mTOR signaling pathway, and is metabolized to Desmethyldoxepin in vivo. Doxepin can be used in research related to various diseases such as depression, anxiety, obesity and atopic dermatitis^[1][2][3][4]. In Vitro: Doxepin exerts protective effects by upregulating the expression of PSD-95 and synapsin 1 through activating the PI3K/AKT/mTOR signaling pathway^[1].
Doxepin is almost ineffective in inhibiting serotonin (5-HT) uptake in rat platelets^[2]. In Vivo: Doxepin (5 mg/kg; p.o.; once daily; for 56 consecutive days) exacerbates obesity, glucose intolerance, non-alcoholic fatty liver disease, renal impairment, and urinary chromium loss in high-fat diet-induced obese C57BL/6J mice. This conclusion is supported by the findings of increased body weight, elevated fatty liver scores, increased blood urea nitrogen levels, enhanced urinary chromium excretion, as well as reduced insulin sensitivity and decreased renal antioxidant enzyme activity^[3].
Doxepin (4.65-24.00 mg/kg; intraperitoneal injection; single administration; 5-120 minutes before electroshock) exerts dose- and time-dependent anticonvulsant activity against maximal electroshock-induced seizures in mice, with the peak efficacy observed at 5 minutes after intraperitoneal administration and an ED₅₀ of 6.6 mg/kg^[4].
Doxepin (6.70-11.63 mg/kg; i.p.; single administration; 5 minutes prior to Isoniazid (HY-B0329) challenge) exhibits anticonvulsant activity against isoniazid-induced seizures in Mus musculus mice, with an ED₅₀ of 8.8 mg/kg and a protective index of 3.0^[4].
Doxepin (3.88-8.04 mg/kg; intraperitoneal injection; single administration; 5 minutes prior to 3-mercaptopropionic acid challenge) exhibits anticonvulsant activity against 3-mercaptopropionic acid-induced seizures in mice, with an ED₅₀ of 5.1 mg/kg and a protective index of 5.2^[4].
Doxepin (4.65-8.04 mg/kg; i.p.; single administration; 5 min prior to Bicuculline (HY-N0219) challenge) exhibits anticonvulsant activity against Bicuculline-induced seizures in mice, with an ED₅₀ of 5.9 mg/kg and a protective index of 4.5^[4].
Doxepin (3.23-5.58 mg/kg; i.p.; single administration; 5 min prior to thiosemicarbazide challenge) exhibits the strongest anticonvulsant activity against thiosemicarbazide-induced seizures in mice, with an ED₅₀ of 4.3 mg/kg and a protective index of 6.1^[4].
Doxepin (24.11-72.00 mg/kg; intraperitoneal injection; single administration; 5-120 minutes before rotarod test) induces time-dependent neurotoxicity in mice by impairing motor coordination, with toxicity peaking at 5 minutes after intraperitoneal administration and a TD₅₀ of 26.4 mg/kg^[4].