This is the first study to investigate CYP2C19 polymorphism in Mexican Americans. The frequencies of the CYP2C19*2 and *3 alleles in Mexican Americans were found to be significantly lower than in other ethnic groups. This genotypic pattern might be responsible for the lower rate of poor metabolizers in Mexican Americans compared with other ethnic groups.

Together, the data reveal unique genetic patterns in Mexican Americans that may be in part responsible for the heightened risk for alcoholism and alcohol-associated health problems in this population.

Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated non-selective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogues were established, and structural–activity relationship studies were carried out. A series of potent and direct agonists of TRPC3/6/ 7 channels were identified, and among them, 4m–4p have a potency order of TRPC3 > C7 > C6, with 4n being the most potent with an EC50 of <20 nM on TRPC3. Importantly, these compounds exhibited no stimulatory activity on related TRP channels. The potent and selective compounds described here should be suitable for evaluation of the roles of TRPC channels in the physiology and pathogenesis of diseases, including glomerulosclerosis and cancer.