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560 Mechanism of ulcerogenic action of 5-hydroxytryptamine in rat's stomach
169
Abstracts of Papers of silicic acid by the technique
described
by Turner
et cd.‘2 1.
W. G. 1. 2. TUNER, I). A., R., FLETCHER, 1%‘. H. (1960), SMITH,
(1961),
3. Pharm. Pharmacol., 13,
Cox, E. V., BALINT, J. A., PIRRIE R. F., HUANG, E. and CEVALLOS, Fed. Pm., 19,876.
559 Central
Action of Certain Drugs upon Gastricwall Dystrophy. I. S. ZAVODSKAYA (U.S.S.R.),
The aim of the present study was to show the mechanism of action of central neurotropic drugs in preventing reflex dystrophy and gastric-ulcer formation induced by excessive irritation of the duodenum. The experiments were carried out on rats and guinea pigs. It is demonstrated that this action is not ascribable to inhibited gastric-juice secretion, as the preventive effect upon reflex impairment of trophic processes in the gastric wall stands in no relation to the intensity of the inhibitive action of the drug. Thus, barbiturates (such as luminal) and certain other anticonvulsants (Dilantin, trimethadione) may, in appropriate dosage, produce the same action upon gastric uice secretion, but luminal is effective, and Dilantin and trimethadione ineffective in preventing reflex dystrophy. The same difference exists between various classes of central cholinolytics. In closes exerting the same inhibitive effect upon gastric-juice secretion, cholinolytics neutralizing arecoline action )e.g. benactyzine) are more effective in preventing reflex dystrophy than those neutralizing nicotine action (e.g. trascntin). An analysis of the EEG obtained enables the author to draw the conclusion that, in the mechanism of central neutropic-drug action upon reflex gastric-wall dystrophy, the most important part is pplayed by the blocking effect upon the upper part of the reticular formation.
560 Mechanism of Ulcerogenic Action of Hydroxytryptamine in Rat’s Stomach. NmonrIev~C and T. TR,\JKOV (Yugoslavia).
5B.
It is a well known fact that 5-HT administered subcutaneously produces gastric erosions and ulcerations in rats. It is also known that LSD-25, BOL-148 or some of the antihistaminic drugs (which have marked antiserotonin properties) prevent the gastric ulcerations normally provoked by serotonin. It was recently shown that iproniazid also prevent \rrotonin gastric ulcers in mice. Our experiments were performed on 53 albino rats of both sexes of 110-150 g body wt., divided into four groups. The first group of 6 animals served only for control determinations of the concentration of histamine (22.5 :-- 2.4-{/g) and rcrotonin ( 1.45 0.07-(/g) in the stomach. The N
second group of 16 animals was treated with 5-HT 20 mg/kg subcutaneously twice on one day only; the animals were sacrificed 6 hr after the second injection. There was an ulcer index of 11; the concentration of histamine in these rats’ stomachs was 15.3 :t~ 1.8 y/g, and of serotonin 3.06 i 0.23 -c/g. The third group of 16 animals was given Antistin (30 mg/kg intraperitoneally four times) on one day, and 5-HT in the same doses and in the same way as the previous group. There was a 4.5 ulcer index; histamine 24.7 x 6 y/g of stomach, and serotonin 3.38 :iI 0.123 y/g. The fourth group of 15 animals was pretreated with iproniazid 100 mg/kg i.p.; 10 hr later ulcerogenic doses of 5-HT were administered. There was an ulcer index of 9.2; histamine-18.2 1 3.2 u/g of stomach and serotonin9.38 -: 0.46 y/g. With regard to the above results, we think that the following may be stated: (1) Antistin (an antihistaminic drug which has almost no antiserotonin properties), considerably reduces the 5-HT provoked gastric ulcers in rats; (2) Iproniazid did not show visible protective effect on gastric ulcer formation: and (3) ulcerogenic action of serotonin on rat’s stomach is the result of the histamine liberating properties of this substance rather than of a direct 5-HT effect on the rat’s gastric mucosa. 561 Structure-Activitv and Enzvme-Substrate Relationships of Ikstamine; Histamine Metabolites and Analogues in Stimulation of Gastric Secretion. T. hl. LIN, F. G. HENDERSON, K. K. CHEN and D. N. BENSLAY (U.S.A.). The structure-activity relationship of 6 histamine metabolitrs and 2 imidazole derivatives (lopyrazole, 13 S-triazole), 2 tetrazole analogues of histamine and 6 miscellaneous /3-aminoethyl compounds on gastric HCl secretion was compared in dogs. The in vitro susceptibility of these agents to histaminasc and its relation to in uivo potentiation of their effects by a histaminase inhibitor were also Linear dose-response relationship was studied. obtained by oral administration of all effective agents resistant to the action of histaminase. COW trary to histamine, the action of these agents on gastric secretion was not augmented by the histaminase inhibitor. The side effects of these products resembled those caused by histamine. Antihistaminics blocked the side effects of histamine and its derivatives but had either no effect or augmented the gastric response of the dog or cat to the same substances. It is postulated that histamine and its metabolitcs or analogues act on the same receptor sites: the receptor sites on the parietal cells arc distinct from the receptor sites for histamine The significance of these in other organs or tissues. findings will be discussecl. Gastric 562 Reserpine and S. EMAS (Sweden). The
mechanism
of’ the
Acid
Secretion.
stimulating
effect
of
Abstracts of Papers of silicic acid by the technique
described
by Turner
et cd.‘2 1.
W. G. 1. 2. TUNER, I). A., R., FLETCHER, 1%‘. H. (1960), SMITH,
(1961),
3. Pharm. Pharmacol., 13,
Cox, E. V., BALINT, J. A., PIRRIE R. F., HUANG, E. and CEVALLOS, Fed. Pm., 19,876.
559 Central
Action of Certain Drugs upon Gastricwall Dystrophy. I. S. ZAVODSKAYA (U.S.S.R.),
The aim of the present study was to show the mechanism of action of central neurotropic drugs in preventing reflex dystrophy and gastric-ulcer formation induced by excessive irritation of the duodenum. The experiments were carried out on rats and guinea pigs. It is demonstrated that this action is not ascribable to inhibited gastric-juice secretion, as the preventive effect upon reflex impairment of trophic processes in the gastric wall stands in no relation to the intensity of the inhibitive action of the drug. Thus, barbiturates (such as luminal) and certain other anticonvulsants (Dilantin, trimethadione) may, in appropriate dosage, produce the same action upon gastric uice secretion, but luminal is effective, and Dilantin and trimethadione ineffective in preventing reflex dystrophy. The same difference exists between various classes of central cholinolytics. In closes exerting the same inhibitive effect upon gastric-juice secretion, cholinolytics neutralizing arecoline action )e.g. benactyzine) are more effective in preventing reflex dystrophy than those neutralizing nicotine action (e.g. trascntin). An analysis of the EEG obtained enables the author to draw the conclusion that, in the mechanism of central neutropic-drug action upon reflex gastric-wall dystrophy, the most important part is pplayed by the blocking effect upon the upper part of the reticular formation.
560 Mechanism of Ulcerogenic Action of Hydroxytryptamine in Rat’s Stomach. NmonrIev~C and T. TR,\JKOV (Yugoslavia).
5B.
It is a well known fact that 5-HT administered subcutaneously produces gastric erosions and ulcerations in rats. It is also known that LSD-25, BOL-148 or some of the antihistaminic drugs (which have marked antiserotonin properties) prevent the gastric ulcerations normally provoked by serotonin. It was recently shown that iproniazid also prevent \rrotonin gastric ulcers in mice. Our experiments were performed on 53 albino rats of both sexes of 110-150 g body wt., divided into four groups. The first group of 6 animals served only for control determinations of the concentration of histamine (22.5 :-- 2.4-{/g) and rcrotonin ( 1.45 0.07-(/g) in the stomach. The N
second group of 16 animals was treated with 5-HT 20 mg/kg subcutaneously twice on one day only; the animals were sacrificed 6 hr after the second injection. There was an ulcer index of 11; the concentration of histamine in these rats’ stomachs was 15.3 :t~ 1.8 y/g, and of serotonin 3.06 i 0.23 -c/g. The third group of 16 animals was given Antistin (30 mg/kg intraperitoneally four times) on one day, and 5-HT in the same doses and in the same way as the previous group. There was a 4.5 ulcer index; histamine 24.7 x 6 y/g of stomach, and serotonin 3.38 :iI 0.123 y/g. The fourth group of 15 animals was pretreated with iproniazid 100 mg/kg i.p.; 10 hr later ulcerogenic doses of 5-HT were administered. There was an ulcer index of 9.2; histamine-18.2 1 3.2 u/g of stomach and serotonin9.38 -: 0.46 y/g. With regard to the above results, we think that the following may be stated: (1) Antistin (an antihistaminic drug which has almost no antiserotonin properties), considerably reduces the 5-HT provoked gastric ulcers in rats; (2) Iproniazid did not show visible protective effect on gastric ulcer formation: and (3) ulcerogenic action of serotonin on rat’s stomach is the result of the histamine liberating properties of this substance rather than of a direct 5-HT effect on the rat’s gastric mucosa. 561 Structure-Activitv and Enzvme-Substrate Relationships of Ikstamine; Histamine Metabolites and Analogues in Stimulation of Gastric Secretion. T. hl. LIN, F. G. HENDERSON, K. K. CHEN and D. N. BENSLAY (U.S.A.). The structure-activity relationship of 6 histamine metabolitrs and 2 imidazole derivatives (lopyrazole, 13 S-triazole), 2 tetrazole analogues of histamine and 6 miscellaneous /3-aminoethyl compounds on gastric HCl secretion was compared in dogs. The in vitro susceptibility of these agents to histaminasc and its relation to in uivo potentiation of their effects by a histaminase inhibitor were also Linear dose-response relationship was studied. obtained by oral administration of all effective agents resistant to the action of histaminase. COW trary to histamine, the action of these agents on gastric secretion was not augmented by the histaminase inhibitor. The side effects of these products resembled those caused by histamine. Antihistaminics blocked the side effects of histamine and its derivatives but had either no effect or augmented the gastric response of the dog or cat to the same substances. It is postulated that histamine and its metabolitcs or analogues act on the same receptor sites: the receptor sites on the parietal cells arc distinct from the receptor sites for histamine The significance of these in other organs or tissues. findings will be discussecl. Gastric 562 Reserpine and S. EMAS (Sweden). The
mechanism
of’ the
Acid
Secretion.
stimulating
effect
of