IN VITRO P-GP EXPRESSION AFTER ADMINISTRATION OF CNS
ACTIVE DRUGS
ALINA CRENGUȚA NICOLAE1#, ANDREEA LETIȚIA ARSENE2#*, VLAD VUȚĂ3#, DANIELA ELENA POPA4#, CARMEN ADELLA SÎRBU5#, GEORGE TRAIAN ALEXANDRU BURCEA DRAGOMIROIU4#, ION-BOGDAN DUMITRESCU6#, BRUNO ȘTEFAN VELESCU7#, ELIZA GOFIȚĂ8#, CRISTINA MANUELA DRĂGOI1#
1“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Biochemistry, 6 Traian Vuia Street, Bucharest, Romania
2“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Microbiology, 6 Traian Vuia Street, Bucharest, Romania
3Institute for Diagnosis and Animal Health, Department of Virology, Bucharest, Romania
4“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Drug Control, 6 Traian Vuia Street, Bucharest, Romania
5“Carol Davila” Central University Emergency Military Hospital, Department of Neurology, 134 Calea Plevnei Street, Bucharest, Romania
6“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Physics and Informatics, 6 Traian Vuia Street, Bucharest, Romania
7“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacology and Clinical Pharmacy, 6 Traian Vuia Street, Bucharest, Romania
8University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Toxicology, 2 Petru Rareș Street, 200349, Craiova, Romania
*corresponding author: andreeanitulescu@hotmail.com
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Abstract:
P-glycoprotein (P-gp) is a transmembrane efflux pump, part of the ABC transporters family (ATP-binding cassette) playing an important
role in the absorption (intestine), distribution (CNS and white blood cells) and elimination (liver, kidney) of xenobiotics, as well as
endogenous products, present in various cell types. The clinical significance of P-gp is depicted by drug resistance of the cells, which
ultimately leads to compromising therapy. Modulating the expression of P-gp transporters could be an effective therapeutic strategy in
mitigating the side effects of neuronal drugs, improving pharmacokinetic and pharmacodynamic properties of the substrates whose
effectiveness is limited by P-gp. In the present study we assessed the influence of several CNS active drugs (valproic acid, risperidone,
thioridazine, fluoxetine, lithium), as well as combinations of these drugs associated with quinidine (a classic inhibitor of the P-gp efflux
pump), on the expression of P-glycoprotein, by means of quantitative indirect immunofluorescence. We assessed the expression of P-gp in
vitro, on the murine neuroblastoma cell line N2a, after the administration of these drugs, as well as their associations. The obtained results
revealed significant changes in the expression of P-gp in the neuroblastoma cell line, denoting the inhibition of the efflux pump. An absolute
novelty, for the current research in the pharmacotherapy field, is the synergistic in vitro potention of the inhibitory effect on the expression of
P-gp, revealed by two of the studied drugs: valproic acid and thioridazine. Of all five studied drugs (valproic acid, risperidone, thioridazine,
fluoxetine, lithium), lithium showed the strongest effect on the expression of P-gp.

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