Quisultidine

Quisultidine (LM 24056) is an orally active phenothiazine derivative with both calmodulin (Calmodulin) inhibitory activity (with a IC₅₀ of 55 μM against porcine calmodulin) and muscarinic acetylcholine receptor (mAChR) ligand activity (with a IC₅₀ of 400 nM). It inhibits gastric acid and pepsin secretion, reduces circulating gastrin levels, and blocks histamine-stimulated gastric acid secretion. Quisultidine can be used in the research of duodenal ulcer^{[1][2][3][4][5][6][7]}. In Vitro:Quisultidine (LM 24056) inhibits basal prolactin secretion from anterior pituitary cells isolated from adult male Sprague-Dawley rats, with a mean IC₅₀ of 57 μM^[7].
Quisultidine (15 min) inhibits the activity of calmodulin-activated cyclic GMP phosphodiesterase in porcine brain, with a mean IC₅₀ of 55 μM^[7].
Quisultidine displaces the binding of [³H] QNB to muscarinic receptors in rat striatal membranes, with an IC₅₀ of 400 nM^[5].
Quisultidine exhibits rare irreversible electrooxidation behavior and does not form stable cation radicals. Its oxidation process generates the metabolite 2-(N,N-dimethylsulfamoyl) phenothiazine, which is capable of forming stable cation radicals^[3]. In Vivo:Quisultidine (LM 24056) (3-30 mg/kg; p.o.; single administration) exhibits 10-fold greater potency in inhibiting Pentagastrin (HY-A0261)-induced gastric acid secretion than in inhibiting basal gastric acid secretion in female Charles River CD rats with pylorus ligation^[5].
Quisultidin (0.6-10 mg/kg; p.o.; single administration) inhibits gastrin-induced gastric acid secretion in Heidenhain pouch hybrid dogs, with an oral ED₅₀ of 1 mg/kg^[5].
Quisultidin (2.5 mg/kg; p.o.; 30 to 50 min before feeding) inhibits feeding-stimulated gastric acid secretion in Heidenhain pouch hybrid dogs, with a duration of action of at least 3 h^[5].
Quisultidin (2.5 mg/kg; p.o.; single administration) exhibits long-acting inhibitory effect on gastrin-induced gastric acid secretion in Heidenhain pouch hybrid dogs, with an inhibition rate of 66% still maintained 20 h after dosing^[5].
Quisultidin (up to 300 mg/kg; p.o.; single administration) exhibits no mydriatic activity in mice^[5].
Quisultidin (100 mg/kg; p.o.; single administration) induces mydriasis in rats, with an oral ED₅₀ of 100 mg/kg^[5].
Quisultidin (1-25 mg/kg; i.p.; single administration) exhibits weak or no inhibitory effect on [³H]QNB binding to muscarinic receptors in the heart (peripheral) and striatum (central) in mice ^[5].
Quisultidin (30-60 mg per dog; p.o.; single administration 2 h before meal) is an effective gastric acid secretion inhibitor in Beagle dogs, in which the oral dose of 60 mg/dog completely eliminates food-induced gastric acid and pepsin secretion, and in all tested gastric stimulation models, both 30 mg/dog and 60 mg/dog doses reduce gastrin levels in a dose-dependent manner without altering histamine concentrations^[6].