Comparative efficacy of diazepam and avizafone against sarin-induced neuropathology and respiratory failure in guinea pigs: influence of atropine dose.
Toxicology
; 188(2-3): 197-209, 2003 Jun 30.
Article
en En
| MEDLINE
| ID: mdl-12767691
This investigation compared the efficacy of diazepam and the water-soluble prodiazepam-avizafone-in sarin poisoning therapy. Guinea pigs, pretreated with pyridostigmine 0.1 mg/kg, were intoxicated with 4LD(50) of sarin (s.c. route) and 1 min after intoxication treated by intramuscular injection of atropine (3 or 33.8 mg/kg), pralidoxime (32 mg/kg) and either diazepam (2 mg/kg) or avizafone (3.5 mg/kg). EEG and pneumo-physiological parameters were simultaneously recorded. When atropine was administered at a dose of 3 mg/kg, seizures were observed in 87.5% of the cases; if an anticonvulsant was added (diazepam (2 mg/kg) or avizafone (3.5 mg/kg)), seizure was prevented but respiratory disorders were observed. At 33.8 mg/kg, atropine markedly increased the seizure threshold and prevented early respiratory distress induced by sarin. When diazepam was administered together with atropine, seizures were not observed but 62.5% of the animals displayed respiratory difficulties. These symptoms were not observed when using avizafone. The pharmacokinetic data showed marked variation of the plasma levels of atropine and diazepam in different antidote combination groups, where groups receiving diazepam exhibited the lowest concentration of atropine in plasma. Taken together, the results indicate that avizafone is suitable in therapy against sarin when an anticonvulsant is judged necessary.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sarín
/
Atropina
/
Inhibidores de la Colinesterasa
/
Antagonistas Muscarínicos
/
Diazepam
/
Dipéptidos
/
Anticonvulsivantes
/
Enfermedades del Sistema Nervioso
Límite:
Animals
Idioma:
En
Revista:
Toxicology
Año:
2003
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Irlanda