Actions of cimetidine and ranitidine at some cholinergic sites: Implications in toxicology and anesthesia

Interaction between succinylcholine and ranitidine in rats

“…ml -j which were substantially lower than the ranitidine concentration (500-1000 ~g-ml -l) needed to elicit neuromuscular blockade in vitro. 2 Peak potentiation observed here with ranitidine may, however, have resulted from its intrinsic neuromuscular blocking activity even at the low doses used since succinylcholine was also present at neuromuscular blocking concentrations and would have reduced the margin of safety of neuromuscular transmission. The antiacetylcholinesterase (ACHE) effect of ranitidine which would have been present at the doses and concentrations of ranitidine used here, 2,9 would also contribute to the observed peak potentiation by elevating acetylcholine concentrations with a consequent potentiation of a depolarizing succinylcholine block.…”

Comparative Effects of Cimetidine and Famotidine on the Vagally Stimulated Acid Secretion in the Isolated Mouse Whole Stomach

“…Recently, Krommer et al (11) also supported this theory, demonstrating that the acid secretion induced by electrical field stimulation in isolated mouse stomach was completely abolished by an H2-an tagonist such as cimetidine and lupitidine, and compound 48/80 also inhibited the secretory response. However, cimetidine has some other effects such as anticholines terase activity, sympathetic ganglion blocking and neuro muscular blocking activities (12). Furthermore, Ishikawa et al (13) reported that cimetidine (1-100 pM) inhibited the acid secretion induced by forskolin, which directly activates adenylate cyclase to increase intracellular cyclic AMP.…”

Antimuscarinic and anticholinesterase activity of cimetidine and ranitidine: clinically significant? [letter]

“…The pharmacological profile of the drugs is determined principally by specific inhibition of histamine H2-receptors, although several adverse effects of the drugs (e.g. mental confusion, gynaecomastia, sexual impotence) and their ability to inhibit the cytochrome P450-dependent mixed function oxidase activity cannot be attributed to H2-receptor antagonism (see Gwee & Cheah, 1986).…”

“…It is now well documented that cimetidine and ranitidine also possess anticholinesterase activity (Gwee & Cheah, 1986;Lee et al, 1985). It would be reasonable to suggest, therefore, that the inherent anticholinesterase activity of cimetidine and ranitidine could contribute to the 30% or so relapse rate in patients on maintenance dosage with the drugs (Misiewicz & Bradbury, 1982) and the reported decrease in their efficacy in inhibiting acid secretion during prolonged therapy (Prichard et al, 1986;Sewing et al, 1978), although such outcome of therapy has been attributed to the development of tachyphylaxis and an up-regulation of H2-receptors (Jones et al, 1988;Prichard et al, 1986).…”

“…Thus, the anticholinesterase activity of cimetidine and ranitidine tends to oppose the inhibitory action of the drugs on gastric acid secretion which could be a plausible explanation for the relapse rate and the decreased efficacy of the drugs in some patients during long term therapy. The anticholinesterase activity of cimetidine and ranitidine can, in fact, also account for several other clinically documented effects of the drugs, including bradycardia, A-V heart block, diarrhoea, mental confusion, flushing, lacrimation and increased lower oesophageal sphincter pressure (Gwee & Cheah, 1986;Physicians' Desk Reference, 1990;Stoelting, 1987).…”