Pharmacological study of a new synthetic potential diuretic

A new synthetic disulfamyl compound with pyrimidine nucleus was studied for its oral diuretic action in both rats and dogs and it was found to have directic activity comparable to that of hydrochlorothiazide, but with the advantage of less augmentation of potassium excretion. Acute toxicity studies revealed that this compound has exceedingly high oral and intraperitoneal LD[50] [>8000 mg/ Kg and 325.6 mg/ Kgm] respectively. Again the subacute toxicity studies confirmed the very low toxicity of this compound as is induced no significant changes in all the parameters studied and was devoided of the hypokalaemic effect produced by hydrochlorothiazide. Pharmacological in vivo and in vitro studies pointed to the potential parasympathomimetic activity of the test compound

Effect of interaction between the tricyclic antidepressant [Doxepin] and the B-adrenoceptor blocker [timolol] on the brain monoamines and systemic arterial blood pressure. [Experimental and clinical study]

Daily oral administration of timolol 5 mg/kgm for 2 weeks in albino rats produced significant increase in whole brain [A] and [NA] concentration while [5-HT] was significantly reduced. Doxepin administration 10 mg/kgm/day orally for 2 weeks induced significant increase of rat whole brain [A] and significant reduction of [NA] and [5-HT]. The effects of concurrent timolol and doxepin administration on brain [A], [NA] and [5-HT] were similar to effects of timolol but of less magnitude. In patients with mild to moderate hypertension timolol oral therapy [10 mg b.i.d.] induced a highly significant reduction of both diastolic and systolic pressures, while doxepin therapy 25 mg b.i.d. orally for 2 weeks alone or concurrently with timolol [10 mg b.i.d.] induced just significant reduction of diastolic pressure but the systolic pressure was insignificantly lowered, these effects were significantly less than the effects of timolol therapy alone. The effects of timolol or doxepin therapy as well as the effects of interaction between them on the arterial blood pressure could be partly explained by the changes induced by these druge in the brain monoamines estimated in the present work

Assessment of anti-inflammatory and analgesic activities on the co-administration of acetyl salicylic acid and ibuprofen in adjuvent-arthritic rats

The effects of interaction between acetyl salicylic acid [300 mg/kgm/day orally for 2 weeks] and ibuprofen [100 mg/kgm/day orally for 2 weeks] were studied in albino rats rendered arthritic by intradermal injection of mycobactrium butyricum. The fluorimetric estimation of plasma cortisol level showed significant elevation following acetyl salicylic acid administration and also following combined ibuprofen and acetyl salicylic acid administration but to a less extent, while ibuprofen alone failed to produce any significant change. Analgesic activity was assessed by analgesymeter test. Acetyl salicylic acid and ibuprofen given seperately or conceurrently produced a highly significant analgesic action which did not differ statistically in various groups. Anti-inflammatory activity was assessed by the paw oedema test, the anti-inflammatory action of ibuprofen was statistically more marked than that of acetyl salicylic acid, but was more or less similar to the effect of concurrent drug administration. It could be concluded that the analgesic action of combined acetyl salicylic acid and ibuprofen administration was not superior to either drug when given alone, and the anti-inflammatory action of combined administration did not differ from that of ibuprofen alone, thus one could suggest that, this form of combined drug therapy has no advantage over ibuprofen alone