Effect of drugs acting on the central nervous system on the lethality in mice of Clostridium perfringens epsilon toxin.
Lethal activity of Clostridium perfringens epsilon toxin was significantly reduced by the prior administration of barbiturates. Phenothiazine derivatives such as chlorpromazine and trifluoperazine and butyrophenone derivatives such as haloperidol and spiperone delayed the lethal effects in mice. Reserpine completely protected mice against the toxin when 10 mg/kg of the drug was administered 24 hr before the injection of the toxin, but did not protect when the same dose of the drug was given within 60 min before the injection of the toxin. Diazepam, apomorphine and gamma-butyrolactone also resulted in a significant increase in the time to death after the toxin. On the other hand, atropine, diphenhydramine, chlorpheniramine and verapamil provided no protection against the toxin. The administration of the toxin resulted in a significant decrease of dopamine levels in the brain, but no effect on levels of epinephrine and norepinephrine. The data suggest that drugs which directly or indirectly inhibit release and receptors of dopamine may lessen the lethal effects of epsilon toxin in mice.
Nagahama
M
M
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Sakurai
J
J
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001427:Bacterial Toxins / Q000493:pharmacokinetics / Q000633:toxicity*; D001463:Barbiturates / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry; D002090:Butyrophenones / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D002394:Catechol O-Methyltransferase / Q000032:analysis; D002395:Catecholamines / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003016:Clostridium perfringens; D003975:Diazepam / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008995:Monoamine Oxidase / Q000032:analysis; D010640:Phenothiazines; D012110:Reserpine / Q000494:pharmacology; D010738:Type C Phospholipases
D014150:Antipsychotic Agents; D001427:Bacterial Toxins; D001463:Barbiturates; D002090:Butyrophenones; D002135:Calcium-Binding Proteins; D002395:Catecholamines; D002491:Central Nervous System Agents; D007457:Iodine Radioisotopes; D010640:Phenothiazines; D012110:Reserpine; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens; D001058:Apomorphine; D015107:4-Butyrolactone; D003975:Diazepam