Continuous infusion of the α7 nicotinic acetylcholine receptor agonist EVP-6124 produces no signs of tolerance at memory-enhancing doses in rats: a pharmacokinetic and behavioral study

Behavioural Pharmacology
Nick P van GoethemGerhard Koenig

Abstract

We investigated whether the effects of acutely administered EVP-6124, an α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, on cognition were maintained after 6-day continuous minipump administration. Performance in a delay-dependent forgetting test was measured in the object recognition task after single-oral doses of 0.3 or 1 mg/kg, or at plasma steady-state concentrations (Css) of 0.6 or 2 ng/ml, which were similar to the efficacious plasma concentrations after single-oral dosing. The 0.3 mg/kg acute dose enhanced memory at a total plasma concentration of ∼0.3 ng/ml at 1-4 h after dosing. Continuous treatment produced total plasma Css values of 0.48 and 1.93 ng/ml on day 6 and enhanced memory. At EVP-6124 plasma concentrations that optimally enhance memory in the object recognition task, tolerance did not develop after 6 days of continuous treatment.

References

Nov 1, 1988·Behavioural Brain Research·A Ennaceur, J Delacour
Mar 25, 2000·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·M R PicciottoV Zachariou
Jul 12, 2011·Biochemical Pharmacology·Tanya L Wallace, Richard H P Porter

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Citations

Feb 6, 2017·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Andrew HaywardJoanna C Neill
Jan 31, 2017·European Journal of Pharmacology·Debra J Post-MunsonJames Herrington
Oct 1, 2015·Pharmacological Reviews·Daniel BertrandDiana Donnelly-Roberts

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