Mechanism of action of reserpine in producing gastric haemorrhage and erosion in the mouse

Gastric haemorrhage was produced regularly in mice within 6 hours of the subcutaneous injection of a large dose (2 to 10 mg./kg.) of reserpine or of deserpidine. Rescinnamine, syrosingopine (SU-3118), and tetrabenazine (Ro 1-9569) were less active. Gastric haemorrhage was also produced within 6 hours when 5-hydroxytryptamine (10 mg./kg.) was injected every half-hour. Neither reserpine nor 5-hydroxytryptamine produced gastric haemorrhage in mice which had been vagotomized by tying the oesophagus at the cardio-oesophageal junction or which had been pre-treated with iproniazid. Amphetamine was less effective than iproniazid in preventing gastric haemorrhage after reserpine, and the following drugs were ineffective: cocaine, methyl phenidate (Ritalin), amarin, caffeine, nikethamide, lysergic acid diethylamide and its 2-bromo derivative (BOL148). Gastric haemorrhage was not observed in mice which had been given substantial doses of atropine or of hexamethonium before reserpine. The incidence of haemorrhage was substantially reduced by treatment with an antacid mixture. It is concluded that reserpine-like drugs cause gastric haemorrhage by a mechanism which has an important central component and which involves the liberation of 5-hydroxytryptamine.

 

Comments:

Based on the provided information, it appears that gastric hemorrhage (bleeding in the stomach) can be induced in mice within six hours of subcutaneous injection of certain drugs, specifically reserpine or deserpidine. The hemorrhage can also be induced by injecting 5-hydroxytryptamine (a neurotransmitter) every half-hour. However, neither reserpine nor 5-hydroxytryptamine caused gastric hemorrhage in mice that had undergone vagotomy (tying of the esophagus) or had been pre-treated with iproniazid (a monoamine oxidase inhibitor).

The prevention or reduction of gastric hemorrhage was observed with certain interventions. Iproniazid was effective in preventing gastric hemorrhage after reserpine, and drugs such as amphetamine, cocaine, methylphenidate (Ritalin), amarin, caffeine, nikethamide, lysergic acid diethylamide (LSD), and its 2-bromo derivative (BOL148) were ineffective in preventing gastric hemorrhage. Atropine or hexamethonium, when given in substantial doses before reserpine administration, also prevented the occurrence of gastric hemorrhage.

Furthermore, treatment with an antacid mixture substantially reduced the incidence of hemorrhage. This suggests that the mechanism by which reserpine-like drugs cause gastric hemorrhage involves a central component and the liberation of 5-hydroxytryptamine.

It is important to note that the information provided seems to be derived from a scientific study or research paper.

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