Pharmacological Analysis of the Therapeutic Effect of Radioprotectors Cystamine and Indralin in the Capacity of Radiomitigators.

The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body 60Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation. Moreover, summation of the radioprotective and therapeutic effects of the radioprotector was revealed under these conditions. In mice and rats, α1-adrenoreceptor blocker terazosin did not abolish the therapeutic effect of indralin administrated after irradiation, but blocked the radioprotective effect of indralin applied prior to irradiation. At the same time, 5-HT2 serotonin receptor blocker tropoxin abolished the therapeutic effect of indralin without affecting its radioprotective activity.

[Effect of unithiol on cystamine toxicity in dogs]. / Vliianie unitiola na toksicheskie éffekty tsistamina u sobak.

In experiments with dogs it was shown that administration of unithiol before administration of cystamine decreases toxic effect of the last: period of excitation induced by cystamine is shortened, the time of emetic reaction decreases and expression of the emetic reaction to this preparation is diminished, the recorded EKG changes of conditions of heart decrease.

Benextramine acts as an irreversible noncompetitive antagonist of U46619-mediated contraction of the rat small mesenteric artery.

We have studied the effects of benextramine on the U46619 (11 alpha,9 alpha-epoxymethano-15S-hydroxy-prosta-5Z,13E-dienoic acid)-mediated contraction of the rat isolated small mesenteric artery. U46619 (10 nM-10 microM) produced a concentration-dependent contraction of the small mesenteric artery. The selective prostanoid TP receptor antagonist, SQ 30,741 ([1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]]-7- [[[[[(oxaheptyl)amino]acetyl]amino]-methyl]-7-oxabicyclo[2.2.1]hep t-2-yl]-5- heptenoic acid; 1 microM), produced a parallel, rightward shift of the U46619 curve with an associated pA2 value of 7.43 +/- 0.09. Treatment of tissues with 100 microM benextramine depressed the maximum response to U46619 in a time-dependent manner. However, neither SQ 30,741 (10 microM) nor U46619 (10 microM) incubation significantly protected against this effect. Thus, benextramine acts as an irreversible noncompetitive antagonist of U46619. The mechanism of this action is not yet clear.

Further investigation of anticoccidial activity of 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine.

The clonidine analog 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine exhibits potent activity against Eimeria tenella infections in chickens. Disease control was abrogated by a selective alpha 2 antagonist, which is consistent with the dependence of such activity upon binding to receptors with characteristics of the vertebrate alpha 2 adrenoceptor. Lack of significant activity against the parasite in tissue culture and our inability to detect significant binding of alpha 2 adrenergic ligands to E. tenella imply that the anticoccidial action may be an indirect effect mediated by the host. Efficacy varied, depending upon the Eimeria species, being greatest for the cecal species E. tenella and less for the intestinal species. The effects described differ substantially from previous accounts of adrenergic actions on parasitic protozoa. The evidence suggests that we have observed a new mechanism of action for antiparasitic drugs.

The effect cystamine on gastric secretion in the rat.

The effects of cystamine on gastric secretion were studied in conscious and anaesthetized rat preparations. In the conscious gastric fistula rat cystamine inhibited the basal acid output but increased pepsin output. This pepsinogogue action was inhibited by both atropine and metiamide. In the anaesthetized rat cystamine stimulated gastric acid output, an effect blocked by cimetidine which had an inhibitory E.D. 50 which was not significantly different from that obtained against histamine-stimulated secretion in this preparation. Atropine at high doses failed to inhibit the response. Depletion of mast cell histamine by compound 48/80 the secretory response to cystamine. In the light of these results possible mechanisms of action for the secretagogue effects of cystamine are discussed.