Design, synthesis and pharmacological evaluation of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid with potential GABA-ergic activity. Part 6. Search for new anticonvulsant compounds.
In the recent study we have extended our investigations to the new anticonvulsant derivatives of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid (GHB). Among the obtained compounds N-benzylamide of alpha-(1,2,3,4-tetrahydroisoquinoline)-GHB (9) has demonstrated activity against maximal electroshock (MES) induced seizures in mice (at 100 mg/kg ip) and in rats (at 30 mg/kg, po dose). Lactone 8 and amide 9 have possessed a weak effect on [3H]-muscimol binding. Molecular modeling studies have revealed that anticonvulsant activity of the alpha-substituted amides of GHB might partially be explained by the orientation of the terminal benzylamide fragment.
Malawska
Barbara
B
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland. mfmalaws@cyf-kr.edu.pl
Kulig
Katarzyna
K
Gajda
Justyna
J
Szczeblewski
Dominik
D
Musiał
Anna
A
Wieckowski
Krzysztof
K
Maciag
Dorota
D
Stables
James P
JP
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004597:Electroshock; D018682:GABA Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000737:chemistry*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D014316:Tritium
D000927:Anticonvulsants; D001593:Benzyl Compounds; D018682:GABA Agents; D006885:Hydroxybutyrates; D014316:Tritium; C111420:4-hydroxybutyric acid; D010433:Pentylenetetrazole