COMPARATIVE ANTICONVULSANT ACTIVITY AND NEUROTOXICITY OF 4-AMINO-N-(2,6-DIMETHYLPHENYL)PHTHALIMIDE AND PROTOTYPE ANTIEPILEPTIC DRUGS IN MICE AND RATS

被引：31

作者：

BAILLEUX, V

VALLEE, L

NUYTS, JP

HAMOIR, G

POUPAERT, JH

STABLES, JP

VAMECQ, J

机构：

[1] CHU LILLE, N FRANCE CTR STUDY CHILDHOOD EPILEPSY, F-59037 LILLE, FRANCE

[2] FAC MED LILLE, F-59045 LILLE, FRANCE

[3] UNIV LOUVAIN, SCH PHARM, DEPT MED CHEM, BRUSSELS, BELGIUM

[4] NINCDS, EPILEPSY BRANCH, PRECLIN PHARMACOL SECT, BETHESDA, MD 20892 USA

来源：

EPILEPSIA | 1995年 / 36卷 / 06期

关键词：

N-PHENYLPHTHALIMIDES; ANTICONVULSANTS; NEUROTOXICITY; SEIZURES; EPILEPSY; PRECLINICAL DRUG EVALUATIONS; DRUG SCREENING;

D O I：

10.1111/j.1528-1157.1995.tb02567.x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We compared the anticonvulsant activity and neurotoxicity of 4-amino-N-(2,6-dimethylphenyl)phthalimide (ADD 213063) with those of phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), ethosuximide (ESM), valproate (VPA), and felbamate (FBM). Evaluation of anticonvulsant properties performed according to well-established procedures in rats and mice showed that ADD 213063 is most effective in protecting animals against maximal electroshock seizures (MES). This anti-MES activity is achieved with nontoxic doses, with the optimal effect recorded in rats dosed orally with anti-MES ED(50) and protective index (PI) values of 25.2 mu mol/kg and > 75, respectively. ADD 213063 protects to a lesser extent against seizures induced by subcutaneous (s.c.) picrotoxin and subcutaneous pentylenetetrazol (PTZ) in mice dosed intraperitoneally and orally, respectively. The profile of anticonvulsant action of ADD 213063 closely parallels that of CBZ.

引用

页码：559 / 565

页数：7

共 10 条

[1]

Putnam TJ, Merritt HH, Experimental determination of the anticonvulsant properties of some phenyl derivatives, Science, 85, pp. 525-526, (1937)

[2]

Merritt HH, Putnam TJ, Sodium diphenylhydantoinate in the treatment of convulsive disorders, JAMA, 11, pp. 1068-1073, (1938)

[3]

Coatsworth JJ, Studies on the clinical efficacy of marketed antiepileptic drugs, (1971)

[4]

Bailleux V, Vallee L, Nuyts JP, Vamecq J, Original anticonvulsant properties of two N‐phenylphthalimide derivatives, Biomed Pharmacother, 47, pp. 463-464, (1993)

[5]

Bailleux V, Vallke L, Nuyts JP, Vamecq J, Anticonvulsant activity of some 4‐amino‐N‐phenylphthalimides and N‐(3‐amino‐2 ethylphenyl) phthalimides, Biomed Pharmacother, 48, pp. 95-101, (1994)

[6]

Krall RL, Penry JK, White BG, Kupferberg HJ, Swinyard EA, Antiepileptic drug development: 11. Anticonvulsant drug screening, Epilepsia, 19, pp. 409-428, (1978)

[7]

Porter RJ, Cereghino JJ, Gladding GD, Et al., Antiepileptic Drug Development Program, Clew Clin J Med, 51, pp. 293-305, (1984)

[8]

Orlof MJ, Williams HL, Pfeiffer CC, Timed intravenous infusion of metrazol and strychnine for testing anticonvulsant drugs, Experimental Biology and Medicine, 70, pp. 254-257, (1949)

[9]

Ramanjaneyulu R, Ticku MK, Interactions of pentamethylenetetrazole and tetrazole analogues with the picrotoxin site of benzodiazepin‐GABA receptor‐ionophore, Eur J Pharmacol, 98, pp. 337-345, (1984)

[10]

Squires RF, Saederup E, Crawley JN, Skolnick P, Paul SM, Convulsant potenties of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain, Life Sci, 35, pp. 1439-1444, (1984)

← 1 →