Anticonvulsant activity of some xanthone derivatives.
A series of appropriate alkanolamine and amide derivatives of xanthone were prepared and evaluated for anticonvulsant activity using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) induced seizures, and for neurotoxicity (TOX) using the rotorod test on mice and rats. The most promising compounds seem to be the appropriate aminoalkanolic derivatives of 6-chloroxanthone, among which the R-(-) and S-(+)-2amino-1-propanol derivatives of 6-chloro-2-methylxanthone (2(a) and 2(b)) displayed anti-MES activity (in mice) with a protective index (TD(50)/ED(50)) of 6.23<6.85, corresponding to that of phenytoin, carbamazepine and valproate. The most active compound, 2(b), was determined to have an affinity to the benzodiazepine (BDZ) receptor and voltage-dependent Ca(2+) channel (VDCC) by using radioligand binding assays. The enantiomeric purities of 2(a) and 2(b) were determined using an analytical liquid chromatography-mass spectrometry method.
Marona
Henryk
H
Jagiellonian University, Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Medyczna 9, 30-688 Cracow, Poland. hen.mar@interia.pl
Pekala
Elzbieta
E
Antkiewicz-Michaluk
Lucyna
L
Walczak
Maria
M
Szneler
Edward
E
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D044004:Xanthones / Q000737:chemistry* / Q000494:pharmacology*
D000927:Anticonvulsants; D044004:Xanthones; D010433:Pentylenetetrazole