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.
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland. mfmalaws@cyf-kr.edu.pl
Barbara
B
Malawska
Katarzyna
K
Kulig
Justyna
J
Gajda
Dominik
D
Szczeblewski
Anna
A
Musiał
Krzysztof
K
Wieckowski
Dorota
D
Maciag
James P
JP
Stables
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