title: Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly(butylcyanoacrylate) nanoparticles as a parenteral controlled release system.
abstract: A novel non-competitive NMDA receptor antagonist MRZ 2/576 is a potent but rather short-acting (5-15 min) anticonvulsant following intravenous administration to mice as estimated by the prevention of maximal electroshock induced convulsions. This is most probably due to a rapid elimination of the drug from the central nervous system by transport processes that are sensitive to probenecid. Intravenous administration of the drug bound to poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 prolongs the duration of the anticonvulsive activity in mice up to 210 min and after probenecid pre-treatment up to 270 min compared to 150 min with probenecid and MRZ 2/576 alone. The results of this study demonstrate that polysorbate 80 coated poly(butylcyanoacrylate) nanoparticles used so far as a delivery system to the brain for drugs that do not freely penetrate the blood brain barrier can also be used as a parenteral controlled release system to prolong the CNS availability of drugs that have a short duration of action.
authors.affiliation: Department of Pharmaceutical Development, Merz+Co., Frankfurt am Main, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Friese
authors.forename: E
authors.initials: E
authors.lastname: Seiller
authors.forename: G
authors.initials: G
authors.lastname: Quack
authors.forename: B
authors.initials: B
authors.lastname: Lorenz
authors.forename: J
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D051379:Mice; D010793:Phthalazines / Q000008:administration & dosage*; D011136:Polysorbates / Q000008:administration & dosage; D011339:Probenecid / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; C112266:MRZ 2-576; D010793:Phthalazines; D011136:Polysorbates; D016194:Receptors, N-Methyl-D-Aspartate; D004659:Enbucrilate; D011339:Probenecid