Tricyclic antidepressant drugs block histamine H2 receptor in brain

Green, J P; Maayani, Saul

doi:10.1038/269163a0

Cited by 233 publications

(58 citation statements)

References 17 publications

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“…In addition to these inconsistencies regarding antidepressant action, there is evidence that tricyclic antidepressants can relieve chronic pain (10 -12). These findings suggest the possibility that biochemical mechanisms (13,14) other than the diverse actions of antidepressants on 5-HT, NE and dopamine synapses may be involved in their clinical effects, including antidepressant activity and pain relief.…”

Section: Discussionmentioning

confidence: 98%

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Asahi

Yonehara

2001

Japanese Journal of Pharmacology

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ABSTRACT-We have conducted this study to elucidate the influence of GABAergic systems on manifestation of pharmacological activity of desipramine using both pharmacological and electrophysiological methods. Desipramine (20 mg /kg, i.p.) significantly blocked the adjuvant-induced thermal hyperalgesia, which was facilitated by treatment with the GABAA antagonist picrotoxin (2 mg/ kg, i.p.) or the GABAB antagonist saclofen (2 mg/kg, i.p.). This analgesic effect of desipramine was antagonized by post-treatment with picrotoxin or saclofen. However, none of these compounds showed any effect in normal animals without adjuvant-induced inflammation. In a slice preparation of the hippocampus, treatment with GABA (10 -5 -5´10 -4 M), baclofen (10 -5 -10 -4 M) or muscimol (10 -5 -10 -4 M) inhibited the field potential evoked in pyramidal neurons by Schaffer collateral stimulation. The inhibitory effect of GABA was facilitated by concurrent application of desipramine, carbamazepine or diazepam at a concentration of 5´10-5 -2´10 -4 M. The rank of order of facilitation is: desipramine > carbamazepine > diazepam. Desipramine also enhanced the inhibitory effect of baclofen and muscimol. These results suggest that desipramine causes GABAergic systems to activate still more, and this phenomenon appears to be involved in manifestation of the pharmacological activity of desipramine such as antinociception.

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Section: Discussionmentioning

confidence: 98%

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Asahi

Yonehara

2001

Japanese Journal of Pharmacology

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“…Several tricyclic antidepressants are known to have antisecretory properties. In the literature, the antisecretory effect of imipra mine was considered to be mediated through blockade of histamine H2-receptors or muscarinic receptors and through uptake inhibition of noradrenaline or serotonin (6). However, the 2-DG or BeCh stimulated gastric secretion was not greatly affected by s.c. administration of imipramine in rats (12).…”

Section: Discussionmentioning

confidence: 99%

“…The compound acts centrally to reduce gastric acid secretion at low doses presumably through uptake inhibi tion of noradrenaline (14). Furthermore, it causes a blockade of histamine H, -receptors (21), H2-receptors (6) and adrenoceptors (6) in the brain or possesses K+ antagonistic activity at the H+/K+ ATPase site of the parietal cell (5). Pirenzepine, which is a tricyclic com pound without antidepressant properties, definitely inhibits gastric acid secretion by blocking muscarinic receptors in the stomach (4).…”

Section: Discussionmentioning

confidence: 99%

“…KW-5805 elicits an antiulcerogenic effect in various experi mental models largely by acting on the de fensive mechanisms (1-3). In contrast, some tricyclic compounds such as pirenzepine, trimipramine and doxepin exert an antiulcero genic effect at least partly through their anti secretory mechanisms; pirenzepine is anti muscarinic (4) and doxepin is K+ antagonis tic at the H+/K+-ATPase site (5) as well as histamine H2-antagonistic (6,7). KW-5805 did not produce behavioral changes such as increased spontaneous motility and produced no antagonism of reserpine-induced de pression in mice at much higher doses than that which produced antiulcerogenic actions (K. Watanabe and S. Yano, unpublished observation).…”

Section: -[2-(diethylamino)ethyl]aminomentioning

confidence: 99%

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Centrally mediated inhibitory effect of 5-(2-(diethylamino)ethyl)amino-5,11-dihydro(1)benzoxepino(3,4-b)pyridine trihydrochloride (KW-5805) on gastric acid secretion in rats.

et al. 1990

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“…In fact, KW-5805 showed an increase of gastric mucus secretion and improved mu cosal microcirculation (27). reported to be effective in the treatment of gastroduo denal ulcers by their antisecretory action mediated through blockade of muscarinic receptors or histamine H2-receptors and uptake inhibition of noradrenaline or serotonin (3,4,28,29). KW-5805, however, has a very weak musucarinic receptor binding (1/30 of pirenzepine) (13) and no effect on H2-receptors and noradrenaline up take (A. Ishii et al, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Effects of KW-5805, a New Antiulcer Agent, on Experimental Gastric and Duodenal Ulcers, Gastric Mucosal Lesions by Necrotizing Agents and Gastric Acid Secretion

Kosaka

Tanaka

Tomaru

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-Effectsof KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 =1 .2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50=4.5-39.8 mg/kg, p.o.). In addition, the cytoprotecive effect of KW-5805 was not affected by indomethacin, but reserved by N-ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3 -10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-in duced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer prop erties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.

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Tricyclic antidepressant drugs block histamine H2 receptor in brain

Cited by 233 publications

References 17 publications

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Centrally mediated inhibitory effect of 5-(2-(diethylamino)ethyl)amino-5,11-dihydro(1)benzoxepino(3,4-b)pyridine trihydrochloride (KW-5805) on gastric acid secretion in rats.

Effects of KW-5805, a New Antiulcer Agent, on Experimental Gastric and Duodenal Ulcers, Gastric Mucosal Lesions by Necrotizing Agents and Gastric Acid Secretion

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