Abstract
The anticonvulsant effects of acetone have been reported in various animal models of epilepsy. We recently demonstrated that other ketone bodies, methyl ethyl ketone (MEK) and diethyl ketone (DEK), suppressed status epilepticus that was induced by lithium-pilocarpine in rat. In the present study, the anticonvulsant effects of MEK and DEK were evaluated by using four different types of mouse seizure models, which were induced by pentylenetetrazole, kainic acid, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), and electroshock. The effects of clonazepam, a typical anticonvulsant, and acetone were also evaluated and compared with MEK and DEK. In this study, MEK (5 and 10mmol/kg, i.p.) and DEK (2.5 and 5mmol/kg, i.p.) produced anticonvulsant activity against all types of seizure models. Furthermore, MEK and DEK showed almost the same potencies against four different seizure models used, while clonazepam showed significant higher ED50 values against kainic acid-induced and electroshock-induced seizure models as compared with the pentylenetetrazole- or DMCM-induced seizure model. In each study, the highest doses of clonazepam (1 or 3mg/kg) did not show clear anticonvulsant effects against the kainic acid- or electroshock-induced seizures. In conclusion, MEK and DEK showed broad-spectra anticonvulsant effects in both chemically- and electroshock-induced experimental seizure models.
| Original language | English |
|---|---|
| Pages (from-to) | 66-71 |
| Number of pages | 6 |
| Journal | European Journal of Pharmacology |
| Volume | 642 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - Sep 2010 |
| Externally published | Yes |
Fingerprint
Keywords
- Anticonvulsant
- Electroshock-induced convulsion
- Kainic acid
- Ketone body
- Methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate
- Pentylenetetrazole
ASJC Scopus subject areas
- Pharmacology
- Medicine(all)
Cite this
Anticonvulsant effects of methyl ethyl ketone and diethyl ketone in several types of mouse seizure models. / Hasebe, Nobuyoshi; Abe, Koji; Sugiyama, Eriko; Hosoi, Rie; Inoue, Osamu.
In: European Journal of Pharmacology, Vol. 642, No. 1-3, 09.2010, p. 66-71.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anticonvulsant effects of methyl ethyl ketone and diethyl ketone in several types of mouse seizure models
AU - Hasebe, Nobuyoshi
AU - Abe, Koji
AU - Sugiyama, Eriko
AU - Hosoi, Rie
AU - Inoue, Osamu
PY - 2010/9
Y1 - 2010/9
N2 - The anticonvulsant effects of acetone have been reported in various animal models of epilepsy. We recently demonstrated that other ketone bodies, methyl ethyl ketone (MEK) and diethyl ketone (DEK), suppressed status epilepticus that was induced by lithium-pilocarpine in rat. In the present study, the anticonvulsant effects of MEK and DEK were evaluated by using four different types of mouse seizure models, which were induced by pentylenetetrazole, kainic acid, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), and electroshock. The effects of clonazepam, a typical anticonvulsant, and acetone were also evaluated and compared with MEK and DEK. In this study, MEK (5 and 10mmol/kg, i.p.) and DEK (2.5 and 5mmol/kg, i.p.) produced anticonvulsant activity against all types of seizure models. Furthermore, MEK and DEK showed almost the same potencies against four different seizure models used, while clonazepam showed significant higher ED50 values against kainic acid-induced and electroshock-induced seizure models as compared with the pentylenetetrazole- or DMCM-induced seizure model. In each study, the highest doses of clonazepam (1 or 3mg/kg) did not show clear anticonvulsant effects against the kainic acid- or electroshock-induced seizures. In conclusion, MEK and DEK showed broad-spectra anticonvulsant effects in both chemically- and electroshock-induced experimental seizure models.
AB - The anticonvulsant effects of acetone have been reported in various animal models of epilepsy. We recently demonstrated that other ketone bodies, methyl ethyl ketone (MEK) and diethyl ketone (DEK), suppressed status epilepticus that was induced by lithium-pilocarpine in rat. In the present study, the anticonvulsant effects of MEK and DEK were evaluated by using four different types of mouse seizure models, which were induced by pentylenetetrazole, kainic acid, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), and electroshock. The effects of clonazepam, a typical anticonvulsant, and acetone were also evaluated and compared with MEK and DEK. In this study, MEK (5 and 10mmol/kg, i.p.) and DEK (2.5 and 5mmol/kg, i.p.) produced anticonvulsant activity against all types of seizure models. Furthermore, MEK and DEK showed almost the same potencies against four different seizure models used, while clonazepam showed significant higher ED50 values against kainic acid-induced and electroshock-induced seizure models as compared with the pentylenetetrazole- or DMCM-induced seizure model. In each study, the highest doses of clonazepam (1 or 3mg/kg) did not show clear anticonvulsant effects against the kainic acid- or electroshock-induced seizures. In conclusion, MEK and DEK showed broad-spectra anticonvulsant effects in both chemically- and electroshock-induced experimental seizure models.
KW - Anticonvulsant
KW - Electroshock-induced convulsion
KW - Kainic acid
KW - Ketone body
KW - Methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate
KW - Pentylenetetrazole
UR - http://www.scopus.com/inward/record.url?scp=77954620824&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954620824&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2010.05.036
DO - 10.1016/j.ejphar.2010.05.036
M3 - Article
C2 - 20553923
AN - SCOPUS:77954620824
VL - 642
SP - 66
EP - 71
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -