RESUMO
Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Acute, subchronic, and chronic studies were conducted in mice, rats, and dogs to establish a preclinical safety profile for this drug. Clinical signs following single intraperitoneal doses included hypoactivity, tremors, decreased muscle tone, ataxia, prostration, and labored breathing. Death was observed after intraperitoneal but not oral administration. A consistent drug-related effect noted in all multiple-dose studies with this compound was decreased body weight and food consumption. The only other consistent change noted in multiple-dose studies with felbamate was an increase in liver weight (relative and absolute) in the rat and dog which was accompanied in some cases by increases in serum enzyme levels. No histopathological changes were observed in the liver that could explain these elevated serum enzyme levels. Based on the results of these studies it was concluded that long-term administration of felbamate in human clinical trials was warranted.
Assuntos
Anticonvulsivantes/toxicidade , Fármacos Neuroprotetores/toxicidade , Propilenoglicóis/toxicidade , Administração Oral , Animais , Anticonvulsivantes/sangue , Cães , Felbamato , Feminino , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/patologia , Dose Letal Mediana , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Fármacos Neuroprotetores/sangue , Tamanho do Órgão/efeitos dos fármacos , Fenilcarbamatos , Propilenoglicóis/sangue , Ratos , Testes de ToxicidadeRESUMO
Delta-9-Tetrahydrocannabinol (THC) was dissolved in propylene glycol and 25, 50, or 100 mg/kg administereed dialy sc to pregnant Charles River Sprague-Dawley rats on days 6-15 of gestation (presence of sperm considered day 1). Maternal weight gain was depressed, but a significant decrease in fetal weight occurred only in the 50 mg/kg group. No malformations were noted, only some abnormalities consisting of several instances of rudimentary 14th rib and soft or spongy spinal cords.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Cannabis/efeitos adversos , Dronabinol/efeitos adversos , Teratogênicos/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Idade Gestacional , Gravidez , Ratos , Costelas/anormalidades , Costelas/efeitos dos fármacos , Medula Espinal/anormalidades , Medula Espinal/efeitos dos fármacosRESUMO
During 1968 consecutive percutaneous transluminal coronary angioplasty (PTCA) procedures, 4 patients (0.2%) suffered a focal central nervous system complication. Two patients had a hemisphere infarct, one a brainstem infarct and one a hemisphere transient ischemic attack. Embolism was the likely mechanism in 3 cases; in 1 air was injected through the guiding catheter, and in 2 post-coronary bypass cases the ascending aorta was "scraped" with the guiding catheter while searching for a graft ostium. In 1 case the event occurred after a successful PTCA during a period of hypotension. Neurologic complications are rare during PTCA but will occasionally occur as the procedure is performed more frequently.