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Titolo:
Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol
Autore:
Fischer, W; Kittner, H; Regenthal, R; Malinowska, B; Schlicker, E;
Indirizzi:
Univ Leipzig, Rudolf Boehm Inst Pharmakol & Toxikol, D-04107 Leipzig, Germany Univ Leipzig Leipzig Germany D-04107 & Toxikol, D-04107 Leipzig, Germany Univ Leipzig, Inst Klin Pharmakol, D-04107 Leipzig, Germany Univ Leipzig Leipzig Germany D-04107 Pharmakol, D-04107 Leipzig, Germany Med Acad Bialystok, Zaklad Fizjol Doswiadczalnej, PL-15230 Bialystok, Poland Med Acad Bialystok Bialystok Poland PL-15230 PL-15230 Bialystok, Poland Univ Bonn, Inst Pharmakol & Toxikol, D-53115 Bonn, Germany Univ Bonn Bonn Germany D-53115 harmakol & Toxikol, D-53115 Bonn, Germany
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 2, volume: 363, anno: 2001,
pagine: 182 - 192
SICI:
0028-1298(200102)363:2<182:AASCBA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-ADRENERGIC AGONISTS; ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SEIZURE; NA+ CHANNELS; SKELETAL-MUSCLE; RAT; MODELS; BRAIN; CELLS; RECEPTORS;
Keywords:
clenbuterol; anticonvulsants; seizure models; whole-cell voltage-clamp; rat cardiomyocytes; sodium channel;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Fischer, W Univ Leipzig, Rudolf Boehm Inst Pharmakol & Toxikol, Hartelstr 16-18, D-04107 Leipzig, Germany Univ Leipzig Hartelstr 16-18 Leipzig Germany D-04107 , Germany
Citazione:
W. Fischer et al., "Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol", N-S ARCH PH, 363(2), 2001, pp. 182-192

Abstract

Clenbuterol, a lipophilic beta (2)-adrenoceptor agonist, was investigated in various seizure models of experimental epilepsy. In the maximal electroshock seizure threshold test, clenbuterol (greater than or equal to4 mg/kg i.p.) increased the electroconvulsive threshold for tonic seizures in mice. In the traditional maximal electroshock seizure (MES) test in mice, ED50 values of 11 mg/kg i.p. or s.c. were determined. In both models, the Pt-receptor antagonist ICI 118.551 did not antagonize the anticonvulsant activity of clenbuterol. Combinations of clenbuterol with standard antiepileptics revealed additive anticonvulsant effects. Repeated administration of clenbuterol (5 mg/kg s.c., twice daily for 14 days) to mice did not significantly influence its anticonvulsant potency or the effectiveness of phenobarbital inthe MES test. In various chemically-induced seizure tests with tonic convulsions, clenbuterol inhibited or tended to suppress the tonic phase. However, this drug was not effective in preventing clonic seizures in the pentylenetetrazol (85 mg/kg s.c.) seizure threshold test. In the rotarod ataxia test (mice), a minimal "neurotoxic" dose (TD50) of 41 mg/kg i.p. was determined. In unrestrained rats with chronically implanted electrodes in the dorsal hippocampus, clenbuterol (2 mg/kg and 4 mg/kg i.p.) significantly reducedthe duration of electrically evoked hippocampal afterdischarges. In amygdala-kindred rats, clenbuterol (5 mg/kg and 10 mg/kg i.p.) reduced the seizure severity to stage 3. Additional studies indicated that clenbuterol (6 mg/kg i.p.) increased the heart rate and decreased the blood pressure, but this drug did not alter the plasma level of the two tested antiepileptics phenobarbital and carbamazepine. Furthermore, in whole-cell voltage-clamp experiments on cultured neonatal rat cardiomyocytes, clenbuterol (1-100 muM) depressed the fast sodium current in a concentration- and frequency-dependent manner. In conclusion, the anticonvulsant effects of higher doses of clenbuterol against generalized tonic-clonic and complex partial seizures seem tobe related to the inhibition of voltage-dependent sodium channels and not to the modulation of beta -adrenoceptors.

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Documento generato il 30/09/20 alle ore 09:42:39