Polymorphic variants of β1 adrenergic receptor gene (Ser49Gly & Arg389Gly) in healthy Tamilian volunteers.

Background & objectives: Several studies reported the polymorphisms of β1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. Methods: The genetic variants were determined by using Taqman 5’ nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. Results: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. Interpretation & conclusions: Our study shows that interethnic variation exists in the polymorphisms of β1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population.

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk.

BACKGROUND: Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension. METHODS: In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension. RESULTS: No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group. CONCLUSIONS: We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene–gene–environment interactions may generate more conclusive claims about the molecular genetics of hypertension.

Effect of ATP sensitive potassium channel modifiers on antinociceptive effect of metoclopramide.

Metoclopramide, a prokinetic drug, has been documented to produce antinociceptive response in animal models through opioid pathways. Morphine has been shown to act through ATP sensitive potassium channels (KATP) to produce antinociceptive response. However, such a possibility has not been examined for metoclopramide. The present study investigated this using pharmacological tools. Acetic acid induced abdominal constriction assay procedure was utilized to assess antinociception. The results confirmed that metoclopramide has antinociceptive response. Glibenclamide, a KATP channel blocker, pretreatment antagonized this response. Where as, in minoxidil pretreated animals, metoclopramide elicited an enhanced antinociceptive response. Glibenclamide and minoxidil, which are known KATP channel blocker and opener respectively, interfered with metoclopramide antinociception. These finding are suggestive of a role for KATP channels in metoclopramide antinociception in mice.

Pharmaco-economic analysis of psychotropic drugs.

OBJECTIVES: To analyse cost and adverse reactions of psychotropic drugs for their cost-effective use. METHODS: Four hundred and sixty nine psychotropic formulations from CIMS, June 1998 were evaluated for (a) extent of variation in retail price for same strength and dosage form, (b) role of number of companies manufacturing the same formulation and (c) companies pricing their product at price less than average of maximum and minimum price in relation to number of products marketed by them. The side effects of antipsychotic and antidepressant drugs were graded for their severity and cumulative side effects score. Side effect index and cost index were calculated on relative basis and their product was used as cost benefit index. RESULTS: Fifty per cent of psychotropic drugs had less than 100% price variation with highest of 2049% for risperidone 4 mg tablets. A direct relationship existed between the drug cost and price variation wherever the variation crossed 200%. Similar trend was noticed between the minimum price variations and the number of companies marketing the product. There was no appreciable relationship between number of products marketed and pricing by the manufacturer. Cumulative side effect score was lowest (10) for trifluoperazine and pimozide and highest (15) for risperidone amongst antipsychotic drugs, whereas amongst antidepressants fluoxetine had lowest (1.75) and amitryptyline had highest (28.5) cumulative side effect score. CONCLUSION: One has to be more careful while selecting a brand of a drug when price variation is more (200-2049%). Trifluoperazine (1.0) and fluoxetine (1.7) were found to be most economical with better cost benefit index compared to thioridazine (494.2) and clomipramine (113.0) in their respective groups. Thus our analysis provides basic information regarding cost effective therapy with psychotropic drugs.