Synthesis and anticonvulsant activity of N-(2-hydroxy-ethyl)amide derivatives.
A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.
Guan
Li-Ping
LP
Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education, Yanji, Jilin, P. R. China.
Zhao
Dong-Hai
DH
Xiu
Jing-Hui
JH
Sui
Xin
X
Piao
Hu-Ri
HR
Quan
Zhe-Shan
ZS
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000209:etiology; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D013329:Structure-Activity Relationship
D000577:Amides; D000927:Anticonvulsants