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Emetic and gastric secretory stimulating action by esters of some amino acids.

Esters of amino acids reduce gastric acidity following intragastric administration but simultaneously exert an emetic effect. A series of experiments was designed on a total of 13 dogs to elucidate the mechanisms of the effects of ethyl-ester of glycine, diethyl-ester of glutamic acid, diisopropyl-ester of glutamic acid, isopropyl-ester of phenylalanine and isobutyl-ester of valine. Oral administration or injection of the esters by means of a gastric cannula with free passage to the duodenum induced emesis in 17 of 23 experiments (74 %) on 6 dogs in an average time of 11 minutes. Occlusion of the duodenum with a Foley catheter distal to the pylorus prevented an emetic response during gastric administration. Emesis was induced in 47/57 administrations (82 %) on 10 dogs 0–10 cm distal to the pylorus by emetic threshold doses within an average time of 8 minutes. Emetic effect declined with distance from the pylorus and below 50 cm no emetic response occurred. The emetic threshold dose in general was 2–4 ml of the esters except for diethyl-ester of glutamic acid, the threshold dose of which was 0.2–0.5 ml. A refractory period of 1–1 1/2 hour's duration to an emetic dose was observed. Hydrochlorides of esters tested showed a similar emetic pattern. In control experiments, copper sulphate induced vomiting from both the stomach and the duodenum in amounts indicating a more potent emetic action (0.025–0.25 g). Diethyl-ester of glutamic acid was also administered intravenously, but amounts 2–6 times larger than the duodenal emetic dose did not evoke emesis. Blockade of the emetic effect was demonstrated by 0.4–2.0 % lidocaine (10–30 ml) and by 0.5–2.0 mg atropine administered locally in the duodenum, whereas the subcutaneous administration of atropine showed a less pronounced blocking effect. Esters of amino acids may act as local irritants. — Gastric administration of 1–2 ml of ester raised the pH to 7.0–7.6 immediately and this lasted for 5–15 min. Neither gastric nor duodenal administration increased the volume or total acid output of innervated or vagally denervated fundic pouches. Perfusion of the isolated, innervated antrum pouch, however, caused an increase of total acid output of the fundic pouch, indicating a release of the antral stimulatory hormone, gastrin.