Anticonvulsant effects of methyl ethyl ketone and diethyl ketone in several types of mouse seizure models.
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-beta-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 10 mmol/kg, i.p.) and DEK (2.5 and 5 mmol/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 ED(50) 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.
Hasebe
Nobuyoshi
N
Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. nobuyoshi.hasebe@shionogi.co.jp
Abe
Kohji
K
Sugiyama
Eriko
E
Hosoi
Rie
R
Inoue
Osamu
O
D000096:Acetone / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D002074:Butanones / Q000494:pharmacology* / Q000627:therapeutic use; D002243:Carbolines / Q000494:pharmacology; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010422:Pentanones / Q000494:pharmacology* / Q000627:therapeutic use; D010433:Pentylenetetrazole / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D002074:Butanones; D002243:Carbolines; D010422:Pentanones; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D000096:Acetone; C005222:methylethyl ketone; C027452:diethyl ketone; D007608:Kainic Acid; D010433:Pentylenetetrazole