Synthesis and anticonvulsant activity of some amino acid derivatives. Part 3: Derivatives of Ala, Arg, Tzl, Gly and chi Abu.
Ten amino acid derivatives as antagonists of the excitatory amino acid (EAA) receptor and anticonvulsant activity have been designed. Five of these compounds supposed to show rather strong and five of them rather weak action as it was expected on the base of their hydrophobicity. All the compounds were synthesized and then evaluated in mice in the maximal electroshock seizure (MES) test, the subcutaneous Metrasol seizure threshold (scMet) test and the rotorod neurotoxicity (Tox) test. Four of the obtained compounds have shown high activity (three received class I and one class II) and six were classified in class III according to the classification of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) of NINDS. One of the compounds classified in class I (10) was tested quantitatively following i.p. administration in mice. It has a MES ED50 = 29.05 b.w. and protective index (PI) of 3.77.
Paruszewski
R
R
Department of Drug Chemistry, Medical University, Warszawa, Poland.
Rostafińska-Suchar
G
G
Strupińska
M
M
Winiecka
I
I
Stables
J P
JP
D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004597:Electroshock; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice
D000596:Amino Acids; D000927:Anticonvulsants