Effect of L-leucinamide hydrochloride on experimental inflammation.

L-leucinamide hydrochloride, an amino acid derivative, was found to share the ability of phenylbutazone in attenuating the phlogistic response induced by intraplantar injection of formaldehyde and nystatin in the unanesthetized rat. In the granuloma pouch induced by the injection of air and croton oil, chronic administration of the drug for 7 days resulted in significant reduction in the volume of exudate and the weight of granulation tissue. While the mechanism of anti-inflammatory action has not been elucidated, it seems that the pituitary-adrenal system is not involved since there was no change in the weight of the adrenals. Of interest is the finding that leucinamide, unlike phenylbutazone, failed to produce gastric ulcers in the effective anti-inflammatory doses.

Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin.

1 The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1 h onwards) there was a progressive decrease in cardiac output, a reduced right atrial filling pressure, systemic hypotension and a profound metabolic acidosis (lactate of 30 +/- 1 mg/100 ml at 5 h compared with 5.1 +/- 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 2 Polymyxin B sulphate, given intravenously (1 min before endotoxin) as a bolus injection (5 mg/kg) followed by a continuous intravenous infusion (additional 5 mg/kg given over a 30 min period) prevented the endotoxin-induced pulmonary (right atrial) hypertension but not the acute systemic hypotension. 3 Polymyxin B sulphate reduced the delayed haemodynamic effects of endotoxin (systemic hypotension, decrease in cardiac output); all the eight animals so treated survived 8 h compared with only 1/8 of the controls. 4 Polymyxin B did not prevent the initial (1-3 h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 5 The mechanism of this marked protective effect of the antibiotic and the possible clinical repercussions are discussed; the most likely explanation for the protection is in chemical combination with the lipid A moiety of the endotoxin.

Effect of creatinine on various experimentally induced inflammatory models.

Creatinine, an aminoacid, has been studied for its anti-inflammatory activity. It is orally effective in suppressing the inflammatory responses produced by carrageenan, 5-hydroxytryptamine, nystatin and formaldehyde. It is observed that the antiinflammatory effect of creatinine is not owing to counter irritant action. It is suggested that it may partially be mediating its anti-inflammatory activity by interfering with the action or/and synthesis of prostaglandins. Like phenylbutazone it also possesses an analgesic action.

Studies on the anti-inflammatory activity of creatine.

Creatine is an aminoacid which has been found to posses anti-inflammatory activity. It is orally effective in modifying the inflammatory response in all of the test models employed. It does not produce gastrointestinal ulceration in the effective doses. In common with many of the nonsteroidal anti-inflammatory agents creatin exhibits analgesic activity. Anti-inflammatory activity is comparable to that of phenylbutazone and merits further studies.

Effect of diethylcarbamazine on Setaria cervi in vitro.

Diethylcarbamazine (DEC) produced an initial stimulation followed by depression of the movements of the intact worm and nerve-muscle preparation of Setaria cervi. The effective concentration of DEC was reduced to one hundredth in the nerve-muscle preparation as compared to the whole worm, suggesting that the cuticular barrier is highly effective in preventing the penetration of the drugs. The depressant effect of DEC was concentration dependent and was not reversed even after repeated changes of the bath fluid. The worms consumed 7.7 mg +/- 0.2 glucose/g wet weight/hr. The consumption of glucose was directly proportional to its motor activity; it increased during the stimulant phase with low doses of DEC and decreased during the depressant phase.

Interaction of quinidine and propranolol in experimental cardiac arrhythmias in the dog.

Quinidine, propranolol and their combination were studied in atrial fibrillation induced by the topical application of acetylcholine or aconitine, injury-stimulation-induced atrial flutter and ventricular ectopic tachycardia produced by coronary occlusion in the dog. The effect of combination of quinidine and propranolol was significantly greater than that of the individual drug in atrial arrhythmias but not in ventricular arrhythmias. The study provides experimental support for the combined clinical use of quinidine and propranolol in the treatment of atrial arrhythmias.

Tremorine-oxotremorine-induced tremor, hypothermia and analgesia, and physostigmine toxicity, in mice after pretreatment with beta-adrenoceptor antagonists.

The beta-adrenoceptor blockers propranolol, PhQA33 and LB-46 exhibited appreciable activity against tremorine-(TMN) and oxotremorine-(OTMN) induced tremor, whereas pronethalol, (+)-H56/28, (-)-H56/28, Kö-592 and L(+)-INPEA possessed weak action. The two beta-blockers, namely D,L(+/-)-INPEA and D(-)-INPEA acted as weak tremorgens. None of the above compounds suppressed the induced peripheral cholinergic phenomena; or possessed any central anticholinergic activity, as they were unable to afford protection against physostigmine-induced death. Propranolol, PhQA33 and LB-46 antagonized TMN-induced hypothermia and analgesia, but were inactive against OTMN-induced changes. A correlation of the beta-blocking and anti-tremor activity of these agents is unlikely.