RESUMO
Three 16-aryloxy analogues of PGF2alpha are potent, full agonists on the isolated rabbit jejunum. Their actions are more prolonged than that of PGF2alpha, and radioactive tracer studies with one of the analogues reveal a slower wash-out of the analogue compared to PGF2alpha, under superfusion conditions. During the prolonged contractile response diminished responses to PGF2alpha were obtained: this effect was investigated in terms of receptor desensitization. The actions of these analogues were also investigated on the isolated guinea-pig ileum and the rabbit oviduct in vivo.
Assuntos
Jejuno/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Prostaglandinas F Sintéticas/farmacologia , Prostaglandinas F/farmacologia , Animais , Fenômenos Químicos , Química , Relação Dose-Resposta a Droga , Tubas Uterinas , Feminino , Cobaias , Íleo/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Prostaglandinas E/administração & dosagem , Prostaglandinas F/administração & dosagem , Prostaglandinas F Sintéticas/administração & dosagem , CoelhosRESUMO
The interaction between delta9-tetrahydrocannabinol (THC) and PGE1 was studied using two pharmacological parameters-the rate of passage of a charcoal meal through mouse small intestine and the abdominal constriction response in the mouse. PGE1 administered intraperitoneally produced a dose-dependent decrease in intestinal motility, and this effect was antagonized by low (0.25 mg/kg) doses of THC and potentiated by higher doses of THC (1 mg/kg). Kinetic analysis suggested that the interaction was of a mixed but predominantly competitive type. PGF2alpha produced an increase in intestinal motility but this was not dose-dependent. THC antagonized the effect of PGF2alpha in a dose-dependent manner suggestive of a physiological antagonism. THC (0.25-2 mg/kg) antagonized the dose-dependent PGE1 abdominal constriction response in a fashion which suggested a mixed (though mainly competitive) antagonism. It would ssem, therefore, that on the two pharmacological parameters studied THC appears to be interacting with PGE1 at the same receptor site. Although the doses of THC used are within the range of those used in man, it is not implied that these results are necessarily implicated in the psychoactivity of the drug.
Assuntos
Analgesia , Cannabis/farmacologia , Dronabinol/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Prostaglandinas E/antagonistas & inibidores , Animais , Ligação Competitiva , Feminino , Cinética , Camundongos , Prostaglandinas E/farmacologia , Prostaglandinas F/antagonistas & inibidoresRESUMO
After oral administration to mice, delta9-tetrahydrocannabinol (THC) and cannabinol (CBN) caused a dose-dependent suppression of the abdominal constriction response to formic acid. Cannabinol was 50 times less active than THC and cannabidiol (CBD) was without effect. The effects of THC and CBN were additive. CBD antagonised the antinociceptive effects of both THC and CBN in a dose-dependent manner.