Napamezole hydrochloride

Napamezole hydrochloride is an orally active α-2 adrenoceptor antagonist and 5-HT (serotonin) reuptake inhibitor, with Ki values of 28 nM and 93 nM for rat α-2 and α-1 adrenoceptors, respectively. It is utilized in the study of depression.

Napamezole (hydrochloride) inhibits the binding of [³H]Clonidine to rat brain α-2 adrenergic receptors with a Kᵢ of 28 nM, and also inhibits the binding of [³H]Prazosin to rat brain α-1 adrenergic receptors with a Kᵢ of 93 nM.

Napamezole (administered orally or via subcutaneous injection) counteracts clonidine-induced analgesia in mice, with an ED₅₀ of 36 mg/kg for oral and 3 mg/kg for subcutaneous administration, indicating its α-2 adrenergic receptor blocking activity in vivo. Additionally, napamezole (30 mg/kg, orally) increases norepinephrine turnover in rat brains, further confirming its α-2 adrenergic receptor blocking capability. When administered intravenously at doses of ≥1 mg/kg, napamezole enhances the firing activity of rat locus coeruleus neurons and reverses clonidine's inhibitory effect on this activity, demonstrating its in vivo α-2 adrenergic receptor blockade.