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Potentiation of pressor effect of tyramine by newly synthesized compound 2[(n- benzylacetamido) mercapto] benzimidazole (vs 25), a putative inhibitor of monoamine oxidaseÃ?¢Ã?â?¬Ã?â??A enzyme in rats | Abstract
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Abstract

Potentiation of pressor effect of tyramine by newly synthesized compound 2[(n- benzylacetamido) mercapto] benzimidazole (vs 25), a putative inhibitor of monoamine oxidaseÃ?¢Ã?â?¬Ã?â??A enzyme in rats

Author(s): Vaishali Madhukar Mute and Subhash Laxmanrao Bodhankar

A series of compounds were synthesized with potential of antidepressant activity. Preliminary research work indicated that monoamine oxidase inhibitor may one of the mechanism of action. Interaction of monoamine oxidase inhibitors with tyramine containing food material is known. Thus aim of the present investigation is to evaluate the pressor effect of tyramine in rats pretreated with synthesized compound (VS 25) and moclobemide. The dose response relationship to tyramine was determined by injecting tyramine i.v. in anaesthetized rats. The study protocol was divided into two parts 1 day treatment model and 14 day treatment model. In one day treatment model, saline control group showed no significant change in SBP,DBP, MABP and heart rate. In cmc control group 1st injection of tyramine showed rise in blood pressure 195.60±8.40 from initial reading of 119.82± 5.62( baseline) before tyramine and subsequent injection decreased blood pressure. Moclobemide 50 mg/kg and VS 25 (30 and 60mg/kg) significantly p<0.01 increased SBP, DBP and MABP. The 14 day treatment model showed significant potentiation of pressor effect of tyramine as compared to 1 day drug treatment model p<0.001. The heart rate decreased in both the model and on 14 day there tachycardia was observed compared to moclobemide. On comparison of 1 day and 14 day treatment model VS 25 (30 mg/kg), VS 25 (60 mg/kg) and moclobemide (50 mg/kg) showed similar rise in SBP, DBP and MABP. Both the drugs failed to prevent tyramine tachyphylaxis. While VS25 (30 mg/kg) showed significant (p<0.001) potentiation of pressor effect of tyramine in 14 day treatment model. Heart rate increased in both VS 25 (30 and 60mg/kg) treated rats. After injection of tyramine (2mg/kg) indicating tachycardia compared to moclobemide and cmc control. Subsequent doses showed mild tachycardia. It is concluded that cardiovascular activity of VS 25 (30 mg/kg) may be due to MAO A inhibition as the potentiation of tyramine pressor response by VS 25 was similar to that of moclobemide.