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P1‐253: Human phase‐1 Multiple Ascending Dose (MAD) study ‐ safety, tolerability and pharmacokinetics of SUVN‐502, a 5‐HT 6 receptor antagonist
Author(s) -
Nirogi Ramakrishna,
Kandikere Vishwottam,
Mudigonda Koteshwara,
Bhyrapuneni Gopinadh,
Jasti Venkat
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.261
Subject(s) - tolerability , pharmacokinetics , pharmacology , adverse effect , antagonist , placebo , medicine , microdialysis , receptor antagonist , psychology , receptor , central nervous system , pathology , alternative medicine
Background: Neuropsychological, clinical, observational and basic science research supports a potential cognitive benefit of soy isoflavones in older adults. While the mechanism remains unclear, mounting evidence from research examining healthy and hypertensive individuals suggests that the cognitive benefits associated with soy isoflavones could be attributed to improvements in vascular function, such as decreased blood pressure, improved lipid profiles, decreased inflammation and restoration of the vasculature. Methods: In order to clarify the potential relation between vascular factors, cognition and soy isoflavones supplements in older adults, we conducted a randomized, placebo-controlled, double-blinded pilot study in 30 men and women (age 62-89 years), using purified glycosidic isoflavones (100 mg/day), in addition to plasma levels of genistein, daidzein and equol over 6 months of treatment. Baseline assessment included blood samples for isoflavone and hormone assays, safety laboratory testing, medical evaluation and neuropsychological testing. Procedures were repeated at months 1, 3 and 6. Results: There were no differences between the groups with regard to sex, age, ApoE status, education, MMSE score or Geriatric Depression score. While similar at baseline, results showed a significant decrease in both systolic (p 1⁄4 .05) and diastolic (p 1⁄4 .02) blood pressure in participants treated with soy isoflavones. Improvement was not observed in measures less closely related with vascular function (temperature, pulse, respirations). Additionally, the groups differed across 6 months of treatment on 8 of 11 cognitive tests. Isoflavones-treated subjects improved on visuospatial memory (p < 0.01), construction (p1⁄4 0.01), verbal fluency (p< 0.01) and speeded dexterity (p 1⁄4 0.04). Interestingly, there was a negative correlation between change in blood pressure and change in verbal performance in the isoflavones treated group, such that participants with the large decreases in blood pressure exhibited the most improved verbal performance (p1⁄4 .06 and p< .01 for systolic and diastolic, respectively). Conclusions: These data offer preliminary support for future investigations of vascular influence on cognitive function in isoflavones research. Specifically, the current study highlights vascular function as a potential mediating variable in the cognition soy isoflavones relationship, and should be considered in future research studies.