Tolazoline (CAS No. 59-98-3) is an imidazoline compound whose core biological activities are antagonizing α?-adrenergic receptors and blocking ATP-sensitive K? channels in pancreatic β cells. It also inhibits cholinergic neurotransmitter release to regulate airway smooth muscle tone and promotes insulin secretion. In terms of IC??/activity parameters, at 10 μM it inhibits 86Rb efflux from mouse islets (reduction of 8.1±0.2%), at 100 μM this inhibition increases to 13.7±0.7%, and at 500 μM it inhibits ATP-sensitive K? channels in pancreatic β cells by about 20%. Reversal of clonidine-induced inhibition of insulin secretion requires concentrations ≥31.8 μM, and the -logK? value for α?-adrenergic receptors in rat cerebral cortex is about 6.80. Common application concentrations: in in vitro experiments, a concentration of 10?? M is used in airway smooth muscle studies to antagonize α? agonist effects, and 10–500 μM gradient concentrations are used in islet function studies. In animal experiments, intravenous injection of 0.12 mg/kg in horses can block xylazine-mediated bronchodilation. Its applications are mainly focused on in vitro pharmacological studies and animal models involving regulation of α?-adrenergic receptor-related pathways. As an α?-adrenergic receptor antagonist, relatively high concentrations are required to exert effects, and its blocking activity on ATP-sensitive K? channels is weaker than that of other imidazoline derivatives.

References:

[1] Ruffolo RR Jr, Messick K, Horng JS. Interactions of dimethoxy-substituted tolazoline derivatives with alpha 1- and alpha 2-adrenoreceptors in vitro. J Auton Pharmacol. 1985 Mar;5(1):71-9. doi: 10.1111/j.1474-8673.1985.tb00567.x. PMID: 2859291.

[2] Jonas JC, Plant TD, Henquin JC. Imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in vitro by inhibiting ATP-sensitive K+ channels in pancreatic beta-cells. Br J Pharmacol. 1992 Sep;107(1):8-14. doi: 10.1111/j.1476-5381.1992.tb14456.x. PMID: 1358388; PMCID: PMC1907631.

[3] LeBlanc PH, Eberhart SW, Robinson NE. In vitro effects of alpha 2-adrenergic receptor stimulation on cholinergic contractions of equine distal airways. Am J Vet Res. 1993 May;54(5):788-92. PMID: 8391231.