Mesaconitine

Mesaconitine is a nitric oxide synthase activator. Mesaconitine drives extracellular Na⁺ and Ca²⁺ influx into endothelial cells, increases intracellular Na⁺ and Ca²⁺ concentrations, and triggers nitric oxide release. Mesaconitine is applicable for pain-related research^[1][2][3]. In Vitro:Mesaconitine (30 μM) induces a sustained increase in [Ca²⁺]ᵢ in HUVECs with a net increase of 361 nM in normal buffer, which is dependent on extracellular Ca²⁺ and Na⁺, inhibited by the reverse-mode Na⁺/Ca²⁺ exchanger inhibitor KBR7943 and the nicotinic acetylcholine receptor inhibitor D-tubocurarine, and unaffected by the Na⁺/H⁺ exchanger inhibitor Cimetidine (HY-14289)^[2].
Mesaconitine (100 μM) induces a small increase in [Na⁺]_i in HUVECs, which is inhibited by the nicotinic acetylcholine receptor inhibitor D-tubocurarine^[2]. In Vivo:Mesaconitine (20-60 μg/kg; s.c.; single dose) produces dose-dependent analgesia in the acetic acid-induced writhing model with an ED₅₀ of 28 μg/kg (s.c.), an effect closely tied to the central noradrenergic system and not mediated via opiate receptors^[3].
Mesaconitine (11 μg/kg; s.c.; single dose) produces dose-dependent central analgesia in the tail flick model with an ED₅₀ of 11 μg/kg^[3].
Mesaconitine (60 μg/kg; s.c.; single dose) modulates central catecholamine levels and turnover in rats, specifically accelerating norepinephrine depletion in select brain and spinal cord regions and dopamine depletion in the striatum when combined with α-methyl-p-tyrosine^[3].