Ranitidine, an inhibitor of gastric acid secretion, competitively antagonizes histamine-induced increases in contraction frequency with a pA2 value of 7.2[1]. Ranitidine inhibits the activity of yeast sucrose enzyme in a non-competitive manner and causes structural changes, with an IC50 value of 2.2mM[2]. Ranitidine attenuates rotenone-induced apoptosis by inhibiting the phosphorylation of JNK and p38, as well as the activation of CASP, thereby preventing the cleavage of PARP and CASP3[3]. Ranitidine has been widely used to inhibit liver regeneration in rats after liver resection and to suppress the cell mitotic activity of liver cells[4].
In vitro, Ranitidine (100µM) pretreatment for 20 minutes significantly inhibited the death of rat cortical neuron cells induced by oxygen-glucose deprivation (OGD), and suppressed the activation of caspase 3 as well as the changes in the cytoskeleton[5]. Treatment with 0.1µM Ranitidine for 48 hours significantly inhibited the growth of Caco-2 cells and induced cell apoptosis[6].
In vivo, Ranitidine treatment via oral administration at a dose of 8mg/kg/day for 8 days significantly reduced the number of CD11b+ Ly6Chi cells in the spleen and bone marrow of BALB/c mice[7]. Oral administration of Ranitidine at a dose of 30mg/kg/day for 14 days significantly increased locomotor exploratory behavior and reduced anxiety-related behavior in a mouse model of gastrointestinal disease[8].
References:
[1] Daly M J, Humphray J M, Stables R. Some in vitro and in vivo actions of the new histamine H2-receptor antagonist, ranitidine[J]. British journal of pharmacology, 1981, 72(1): 49.
[2] Minai-Tehrani D, Ghaffari M, Sobhani-Damavandifar Z, et al. Ranitidine induces inhibition and structural changes in sucrase[J]. Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, 27(4): 553-557.
[3] Park H J, Kim H J, Park H K, et al. Protective effect of histamine H2 receptor antagonist ranitidine against rotenone-induced apoptosis[J]. Neurotoxicology, 2009, 30(6): 1114-1119.
[4] Kanashima R, Nagasue N, Sakato K. Ranitidine as an inhibitor of liver regeneration[J]. The American journal of surgery, 1985, 149(2): 223-227.
[5] Malagelada C, Xifró X, Badiola N, et al. Histamine H2-receptor antagonist ranitidine protects against neural death induced by oxygen-glucose deprivation[J]. Stroke, 2004, 35(10): 2396-2401.
[6] Rajendra S, Mulcahy H, Patchett S, et al. The effect of H2 antagonists on proliferation and apoptosis in human colorectal cancer cell lines[J]. Digestive diseases and sciences, 2004, 49(10): 1634-1640.
[7] Vila-Leahey A, Oldford S A, Marignani P A, et al. Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice[J]. Oncoimmunology, 2016, 5(7): e1151591.
[8] Selvaraj D B, Vergil Andrews J F, Anusuyadevi M, et al. Ranitidine alleviates anxiety-like behaviors and improves the density of pyramidal neurons upon deactivation of microglia in the CA3 region of the hippocampus in a cysteamine HCl-induced mouse model of gastrointestinal disorder[J]. Brain Sciences, 2023, 13(2): 266.