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[P4–588]: EVALUATION OF THE NEUROPROTECTIVE EFFECT OF INTEPIRDINE IN AN IN VITRO OXYGEN/GLUCOSE DEPRIVATION‐INDUCED CYTOTOXICITY MODEL
Author(s) -
Asare Ebenezer,
Roeloffs Rosemarie,
Sampey Brante P.,
Ramaswamy Shankar,
Bruinsma Bote,
Murck Harald,
Friedhoff Lawrence
Publication year - 2017
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.2017.07.751
Subject(s) - neuroprotection , antagonist , pharmacology , nmda receptor , receptor antagonist , medicine , vascular dementia , endocrinology , chemistry , receptor , dementia , disease
by in-vitro dissolution, permeability study (everted intestine sac method), and in-vivo oral pharmacokinetic study using rats. Also, its safety and efficacy were evaluated after 3 months of treatment by oral administration. Results:The soluplus based NEF displayed dramatic improvement in aqueous solubility (17.53-fold) and stability due to amorphization, hydrogen bonding interaction and micellization. Moreover, the NEF demonstrated significant improvement in intestinal permeability and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2, 16.1 and 14.8-fold enhancement compared to EDR suspension at 46, 138 and 414 mM/kg dose. Besides, our data confirms non-toxicity up to 414 mM/kg dose after 3 months and its potential to reverse AD-like cognitive deficits of APP/PS1 mice in dose dependent manner. Conclusions:NEF has great potential to mitigate the limitation associated with EDR and can pave the way for its clinical development for the treatment of AD.