Neuroleptanalgesic “Thalamonal”の薬理学的研究(1)

Abstract

Neuropharmacological properties of Thalamonal were investigated and compared with those of Fentanyl, Droperidol and Morphine. The following results were obtained. 1. Muscle relaxation and the impairment of the posture maintenance, muscle coordination and placing, hopping and righting reflexes were observed following i. v. administration of 0.1ml/kg of Thalamonal in dogs and cats. In addition, threshold for eliciting the nociceptive reactions by natural stimulation was elevated without any noticeable central excitatory symptom. 2. No anti-cardiazol and strychnine convalsive effects or anti-electroshock activity were shown. Thiobarbital anesthesia was potentiated by Thalamonal in mice. Thalamonal was suppressive of apomorphine induced vomiting in dog and also had a slight hypothermic activity at 0.37ml/kg in rabbit. 3. The ED50s of analgesic activity in mice measured by Haffner's method were 0.32ml/kg, 0.087mg/kg for Thalamonal and Fentanyl, respectively, Fentanyl possessed an analgesic potency about 100 times as strong as that of Morphine. 4. In rabbit with chronically implanted electrodes “pain reactions” were induced by tooth pulp stimulation. Doses at which the threshold values were doubled were 0.6ml/kg, 0.03mg/kg, and 10mg/kg for Thalamonal, Fentanyl and Morphine, respectively. Droperidol was not effective at 1.5mg/kg. This threshold elevating effect was shortlasting. 5. By small doses of Thalamonal the EEG activity of both acute and chronic rabbits showed the tendency that the spindle burst waves became frequent, slow waves of high amplitude dominant in the cortex and the theta wave activity was abolished and slow wave became dominant in the hippocampus. Threshold for the EEG arousal response by brain stimulation became higher. 6. In the cat slowly developing potentials of the CM nucleus of the Thalamus evoked by the stimulation of the splanchnic nerve and the canine tooth pulp were abolished by 1.0ml/kg Thalamonal and 0.1mg/kg Fentanyl but rapidly developing evoked potentials of the cortical first and second somatosensory areas from the tooth pulp were not influenced. 7. The direct cortical response at the neocortex was almost uninfluenced even by 2.0ml/kg of Thalamonal.