Effects of misoprostrol on pentylenetetrazol-induced seizures in mice

Medeiros, Francisco das Chagas; Medeiros, Maria Angelina; Rao, Vietla Satyanarayna; Figueiredo, Eberval Gadelha

doi:10.1590/S0004-282X1997000500001

Abstracts

The effects of prostaglandin E - analogue misoprostol on the susceptibility to pentilenetetrazol(PTZ) - induced seizures were examined in mice. Misoprostol (200-800 mg/kg), given subcutaneously 45 min before the subconvulsive dose of PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100%) and mortality in mice. At 300 g/kg, s.c, misoprostol pretreatment significantly (p<0.05) lowered the onset latency to first convulsion as well as the latency to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose misoprostol was found to lower the CD50 and Ld50 values for PTZ by 21 % and 36% respectively. The results suggest that prostaglandins are likely to lower the threshold for convulsions.

seizures; pentylenetetrazol; misoprostol; mice

Os efeitos do misoprostrol, um análogo da prostaglandina E, sobre convulsões induzidas por pentilenotetrazol (PTZ) foram estudados em camundongos. Misoprostrol (200-800 mg/Kg) administrado por via subcutânea 45 minutos antes da dose subconvulsiva de PTZ (30 mg/Kg, i.p.) provocou crises tônico-clônicas (30 a 100%) de maneira dose-dependente e mortalidade em camundongos. Na dose de 300 g/Kg, s.c., o pré-tratamento com misoprostrol diminuiu significativamente (p<0,05) o período de latência da primeira convulsão bem como a mortalidade induzida por uma dose convulsiva de PTZ (60 mg/Kg, i.p.). Nesta dose o misoprostrol diminuiu 21 % e 36% os valores de CD50 e de LD50 do PTZ, respectivamente.

convulsões; pentilenotetrazol; misoprostrol; camundongos

Effects of misoprostrol on pentylenetetrazol-induced seizures in mice

Efeitos de misoprostrol sobre convulsões induzidas por pentilenotetrazol em camundongos

Francisco das Chagas Medeiros; Maria Angelina Medeiros; Vietla Satyanarayna Rao; Eberval Gadelha Figueiredo

Departamento de Fisiologia e Farmacologia - Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza - Brasil

ABSTRACT

The effects of prostaglandin E - analogue misoprostol on the susceptibility to pentilenetetrazol(PTZ) - induced seizures were examined in mice. Misoprostol (200-800 mg/kg), given subcutaneously 45 min before the subconvulsive dose of PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100%) and mortality in mice. At 300 g/kg, s.c, misoprostol pretreatment significantly (p<0.05) lowered the onset latency to first convulsion as well as the latency to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose misoprostol was found to lower the CD₅₀ and Ld₅₀ values for PTZ by 21 % and 36% respectively. The results suggest that prostaglandins are likely to lower the threshold for convulsions.

Key-words: seizures, pentylenetetrazol, misoprostol, mice.

RESUMO

Os efeitos do misoprostrol, um análogo da prostaglandina E, sobre convulsões induzidas por pentilenotetrazol (PTZ) foram estudados em camundongos. Misoprostrol (200-800 mg/Kg) administrado por via subcutânea 45 minutos antes da dose subconvulsiva de PTZ (30 mg/Kg, i.p.) provocou crises tônico-clônicas (30 a 100%) de maneira dose-dependente e mortalidade em camundongos. Na dose de 300 g/Kg, s.c., o pré-tratamento com misoprostrol diminuiu significativamente (p<0,05) o período de latência da primeira convulsão bem como a mortalidade induzida por uma dose convulsiva de PTZ (60 mg/Kg, i.p.). Nesta dose o misoprostrol diminuiu 21 % e 36% os valores de CD50 e de LD50 do PTZ, respectivamente.

Palavras-chave: convulsões, pentilenotetrazol, misoprostrol, camundongos.

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Aceite: 28-julho-1997.

Dr Eberval Gadelha Figueiredo - Rua Alves Guimarães 461 Apto 41 - 05410-000 São Paulo SP - Brasil.

1. Anderson GG, Steege JF. Clinical experience using intramniotic prostaglandins F2alpha for midtrimester abortion in 600 patients. Obstet Gynecol 1975;46:591-595.
2. Brandenburg H, Jahoda MG, Wladimiroff JW, Los FJ, Lindhout D. Convulsions in epileptic women after administration of prostaglandin E2 derivate . Lancet 1990;336:1138.
3. Folco GC, Longiave D, Bosisio E. Relations between prostaglandin E2, F2alpha and cyclic nucleotides levels in rat brain and induction of convulsions. Prostaglandins 1977;13:893-900.
4. Forsterman U, Heldt R, Knappen F, Hertting G. Potential anticonvulsive properties of endogenous prostaglandins formed in mouse brain . Brain Res 1982;240:303-310.
5. Hendricks CH, Brenner WE, Ekbladh L, Brotanek V, Fishburne JI Jr. Efficacy and tolerance of intravenous prostaglandins F2 and E2. Am J Obstet Gynecol 1971 ;111:564-579.
6. Karim SM, Trussell RR, Hillier K, Patel RC. Induction of labour with prostaglandin F2a. J Obstet Gynaecol Br Commonw 1969;76:769-770.
7. LaFerla, JJ. Midtrimester abortion: techniques and complications. Clin Perinatol 1983;10:305-320.
8. Lauersen NH. Termination of midtrimester pregnancy by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha. Am J Obstet Gynecol 1976;124:169-176.
9. Millichap JG. Relation of laboratory evaluation to clinical effectiveness of antiepileptic drugs. Epilepsia 1969; 10:315-328.
10. Rastogi SK, Puri JN, Sinha JN, Bhargava KP. Involvement of central cholinoceptors in Metrazol-induced convulsions. Psychopharmacology 1979;65:215-217.
11. Steinhauer HB, Hertting G. Lowering of the convulsive threshold by non-steroidal anti-inflamatory drugs. Eur J Pharmacol 1981;69:199-203.
12. Wallenstein MC, Mauss EA. Effect of prostaglandin synthetase inhibitors on experimentallly induced convulsions in rats. Pharmacology 1984;29:85-93.
13. Wiqvist N, Bygdeman M. Induction of therapeutic abortion with intravenous prostaglandin F. Lancet 1970; 1:889.
14. Wolfe LS, Coceani F. The role of prostaglandins in the central nervous system. Ann Ver Physiol 1979;41:669-684.

Publication Dates

Publication in this collection
21 Oct 2010
Date of issue
1997

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Anderson GG, Steege JF. Clinical experience using intramniotic prostaglandins F2alpha for midtrimester abortion in 600 patients. Obstet Gynecol 1975;46:591-595.

[2] 2. Brandenburg H, Jahoda MG, Wladimiroff JW, Los FJ, Lindhout D. Convulsions in epileptic women after administration of prostaglandin E2 derivate . Lancet 1990;336:1138.

[3] 3. Folco GC, Longiave D, Bosisio E. Relations between prostaglandin E2, F2alpha and cyclic nucleotides levels in rat brain and induction of convulsions. Prostaglandins 1977;13:893-900.

[4] 4. Forsterman U, Heldt R, Knappen F, Hertting G. Potential anticonvulsive properties of endogenous prostaglandins formed in mouse brain . Brain Res 1982;240:303-310.

[5] 5. Hendricks CH, Brenner WE, Ekbladh L, Brotanek V, Fishburne JI Jr. Efficacy and tolerance of intravenous prostaglandins F2 and E2. Am J Obstet Gynecol 1971 ;111:564-579.

[6] 6. Karim SM, Trussell RR, Hillier K, Patel RC. Induction of labour with prostaglandin F2a. J Obstet Gynaecol Br Commonw 1969;76:769-770.

[7] 7. LaFerla, JJ. Midtrimester abortion: techniques and complications. Clin Perinatol 1983;10:305-320.

[8] 8. Lauersen NH. Termination of midtrimester pregnancy by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha. Am J Obstet Gynecol 1976;124:169-176.

[9] 9. Millichap JG. Relation of laboratory evaluation to clinical effectiveness of antiepileptic drugs. Epilepsia 1969; 10:315-328.

[10] 10. Rastogi SK, Puri JN, Sinha JN, Bhargava KP. Involvement of central cholinoceptors in Metrazol-induced convulsions. Psychopharmacology 1979;65:215-217.

[11] 11. Steinhauer HB, Hertting G. Lowering of the convulsive threshold by non-steroidal anti-inflamatory drugs. Eur J Pharmacol 1981;69:199-203.

[12] 12. Wallenstein MC, Mauss EA. Effect of prostaglandin synthetase inhibitors on experimentallly induced convulsions in rats. Pharmacology 1984;29:85-93.

[13] 13. Wiqvist N, Bygdeman M. Induction of therapeutic abortion with intravenous prostaglandin F. Lancet 1970; 1:889.

[14] 14. Wolfe LS, Coceani F. The role of prostaglandins in the central nervous system. Ann Ver Physiol 1979;41:669-684.