Archives internationales de pharmacodynamie et de thérapie
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Arch Int Pharmacodyn Ther · Nov 1989
Pirenzepine prevents cysteamine-induced formation of gastroduodenal ulcers and reduction of mesenteric circulation.
The effects of pirenzepine on gastric and duodenal ulceration and barrier mucus levels, as well as on changes of superior mesenteric artery diameter caused by cysteamine, were investigated in rats and compared with those of atropine. Cysteamine induced severe gastric and duodenal ulcers and decreased both barrier mucus levels and mesenteric blood flow. Pirenzepine reduced gastric and duodenal ulceration induced by cysteamine. ⋯ The present results are consistent with the view that pirenzepine protects against gastroduodenal ulceration caused by cysteamine by increasing blood flow at the level of the ulcerated mucosa. The higher affinity of pirenzepine for the muscarinic receptors of sympathetic ganglia may explain the difference between the effects of pirenzepine and atropine. In addition to this, the measurement of superior mesenteric artery diameter changes may represent an accurate and reproducible method, suitable for studying the gastrointestinal protective mechanisms of the drugs.
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Arch Int Pharmacodyn Ther · Nov 1989
Lack of importance of caffeine as an analgesic adjuvant of dipyrone in mice.
The analgesic effect of caffeine used alone and in combination with dipyrone and butalbital was evaluated after oral administration in mice, using two different pain tests: the hot plate test and the phenylbenzoquinone-induced writhing test. Neither caffeine (5 to 200 mg/kg) nor butalbital (10 and 20 mg/kg) (20 mg/kg was the highest dose that did not induce sleep) produced a significant antinociceptive effect, whereas dipyrone was active from 400 mg/kg in the hot plate test and from 50 mg/kg in the writhing test. The scores obtained with the combinations were not different from those of the dipyrone-treated group, except for the butalbital-dipyrone combination. Thus caffeine is not an analgesic adjuvant in mice; its presence in the combination studied appears to be justifiable only insofar as it inhibited the sedative effect of butalbital.
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Arch Int Pharmacodyn Ther · Nov 1989
Comparative StudySome effects of desmethylimipramine and amitriptyline on the schedule-controlled behavior of pigeons and rats.
The effects of desmethylimipramine and amitriptyline on schedule-controlled behavior of pigeons and rats were examined. Pigeons responded under either a multiple (mult) fixed-interval (FI) 600-sec, fixed-ratio (FR) 30-response schedule of food presentation or a mult FI 200-sec, FI 200-sec schedule, in which responding during one component was punished with electric shock. Rats responded under a mult FI 300-sec, FR 30-response schedule of food presentation. ⋯ In contrast, in the rat desmethylimipramine and amitriptyline did not differentially affect the low rates of responding at the beginning of the FI compared to the higher rates of responding at the end of the FI. Correspondingly, in the pigeon, but not in the rat, desmethylimipramine and amitriptyline decreased the fixed-interval quarter-life at relatively low doses. In the pigeon neither desmethylimipramine nor amitriptyline differentially affected the overall rate of punished as compared to unpunished responding.
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Arch Int Pharmacodyn Ther · Dec 1987
Digoxin-induced cardiac toxicity in the anaesthetized guinea-pigs and effect of heparin infusion.
We have examined the effects of heparin infusion on the arrhythmias induced by digoxin. Digoxin treatment consisted of 0.6 mg kg-1 given i.v. 15 min after the beginning of heparin infusion. ⋯ Heparin at the infusion rates of 3.4 IU and 6.8 IU kg-1.min-1 reduced significantly the arrhythmia scores. On the other hand, heparin did not significantly alter the arterial blood pressure and heart rate values affected by digoxin.
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Arch Int Pharmacodyn Ther · Oct 1987
Evidence for central alpha 2-adrenoceptor-mediated hypertension in freely moving, normotensive rats.
The hypertensive response mediated by central alpha 2-adrenoceptor stimulation was investigated in freely moving, normotensive rats with chronic arterial catheters and guide cannulas. The alpha 1-adrenoceptor agonists (methoxamine, phenylephrine, ST 587) and the alpha 2-adrenoceptor agonists (B-HT 920, clonidine, oxymetazoline) injected intravenously (i.v.) caused a rise in mean blood pressure. The rank order of potency of the agonists to produce 25 mm Hg of pressor response (the effective dose; ED25) was oxymetazoline (0.64 microgram/kg) greater than phenylephrine (1.05 microgram/kg) greater than clonidine (1.6 microgram/kg) greater than ST 587 (5.4 micrograms/kg) greater than B-HT 920 (19.0 micrograms/kg) greater than methoxamine (19.5 micrograms/kg). ⋯ The rank order of potency of the agonists injected i.c.v. in producing pressor responses with ED25 was clonidine (12.0 micrograms/kg) greater than oxymetazoline (14.0 micrograms/kg) greater than B-HT 920 (16.0 micrograms/kg) much greater than ST 587 (125 micrograms/kg) greater than phenylephrine (235 micrograms/kg) greater than methoxamine (310 micrograms/kg). Central (i.c.v.) pretreatment with yohimbine (100 micrograms/kg) abolished hypertensive responses to centrally administered alpha 2-adrenoceptor agonists but the treatment with prazosin (30 micrograms/kg) was less effective in inhibiting the hypertensive responses. In pentobarbital-anesthetized rats, pressor responses to i.c.v. injection of alpha 1- and alpha 2-adrenoceptor agonists were significantly inhibited and a long-lasting depressor response was induced by alpha 2-adrenoceptor agonists, whereas depressor responses to alpha 1-adrenoceptor agonists were not affected.(ABSTRACT TRUNCATED AT 400 WORDS)