Assuntos
Acetilcolinesterase/sangue , Compostos de Decametônio/farmacologia , Reativadores Enzimáticos , Compostos Organofosforados/farmacologia , Compostos de Piridínio/farmacologia , Animais , Inibidores da Colinesterase , Interações Medicamentosas , Eritrócitos/enzimologia , Humanos , Técnicas In Vitro , Oximas/farmacologia , Coelhos , Sarina/farmacologia , Soman/farmacologiaAssuntos
Acetilcolina/metabolismo , Atropina/farmacologia , Química Encefálica/efeitos dos fármacos , Intoxicação por Organofosfatos , Fisostigmina/farmacologia , Soman/intoxicação , Animais , Encéfalo/enzimologia , Inibidores da Colinesterase , Interações Medicamentosas , Masculino , Neostigmina/farmacologia , RatosAssuntos
Reativadores da Colinesterase , Colinesterases/metabolismo , Intoxicação por Organofosfatos , Compostos de Pralidoxima/farmacologia , Soman/intoxicação , Animais , Atropina/farmacologia , Inibidores da Colinesterase/farmacologia , Dose Letal Mediana , Masculino , Brometo de Piridostigmina/farmacologia , Coelhos , Fatores de TempoAssuntos
Acetilcolina/metabolismo , Atropina/farmacologia , Química Encefálica/efeitos dos fármacos , Carbamatos/farmacologia , Mecamilamina/farmacologia , Compostos Organofosforados/antagonistas & inibidores , Soman/antagonistas & inibidores , Animais , Benactizina/farmacologia , Masculino , Neostigmina/farmacologia , Fisostigmina/farmacologia , Coelhos , Ratos , Soman/intoxicação , Fatores de TempoRESUMO
The toxicity (LD50) of several carbamates, all reversible inhibitors of cholinesterase (ChE), were determined in male rabbits. These include isopropyl methylphenyl carbamate (IMPC), pyridostigmine, neostigmine, benzpyrinium and physostigmine. When 1/9 of the LD50 of the above carbamates was individually combined with atropine (A) and benactyzine (B), mecamylamine (M) or chloropromazine (CPZ) and administered to rabbits in a pretreatment regimen, most animals could be protected from a 10 LD50 challenge of Soman. If CPZ, M or B was omitted from this regimen, no rabbits survived this challenge of Soman. The protection afforded against Soman was found to be related to reversible inhibition of ChE by the carbamates; reversible ChE inhibition varied with the route of injection and with the physical properties of the carbamate. Oral administration of pyridostigmine, a quaternary carbamate, provided protection for 24 hours. When the pretreatment included four components (pyridostigmine, A, M and B), the LD50 of Soman was raised 30.8 times in rabbits.
Assuntos
Carbamatos/farmacologia , Colinesterases/sangue , Compostos Organofosforados/antagonistas & inibidores , Soman/antagonistas & inibidores , Animais , Carbamatos/toxicidade , Dose Letal Mediana , Masculino , Brometo de Piridostigmina/farmacologia , Coelhos , Soman/toxicidadeRESUMO
Soman reduced blood and brain cholinesterase (ChE) activity to less than 15% and increased cerebral acetylcholine (ACh) levels to 137.4% of control. When pyridostigmine (P) was used as a prophylactic adjunct, it reduced blood ChE activity to 31.6% of control, failed to significantly alter brain ChE activity, and protected more than 70% of the blood (but not brain enzyme) from phosphonylation by soman. Benactyzine (B) was more effective than atropine (A) in reducing cerebral ACh concentrations, while a combination of the two was more effective than either alone. A prophylaxis of P + A + B was effective in controlling ACh levels in rats poisoned with one LD50 dose of Soman. Since P did not diminish the effects of the cholinolytics on cerebral ACh, this (together with the enzyme data) suggests that the two cholinolytics alone provided the central protection.