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In a rat model of volume-controlled hemorrhagic shock causing the death of all saline-treated animals within 30 min of treatment, the intravenous bolus injection of thyrotropin- releasing hormone tartrate (TRH-T) at the dose of 4 mg/kg induced the prompt and sustained disappearance of the ECG and EEG signs of heart and brain ischemia, along with the reversal of hypotension and respiratory depression and with 100% survival rate at the end of the 2 h observation period. These data confirm that, in a pre-terminal condition induced by massive hemorrhage, timely treatment with TRH-T will restore heart and brain perfusion to levels compatible with survival and with functional recovery from ischemia and maintain it at those levels for some hours.

Intraperitoneal injection of putrescine induced dose-related hypothermia in rats. The effect was more pronounced at room temperature (22 degrees C) than in a warm environment (30 degrees C), the maximum hypothermia (-2.64 +/- 0.29 degrees C, 30 min. after treatment) being obtained with the dose of 300 mg/Kg and remaining significant throughout 3 hr of observation. Putrescine also had antipyretic activity, as it significantly reduced pyrogen-induced fever at a dose level (100 mg/Kg i.p.) ineffective in causing hypothermia in normal rats. The hypothermic and antipyretic effects of putrescine were not associated with any obvious sign of toxicity.

alpha-Difluoromethylornithine (DFMO) directly infused into a brain-lateral ventricle (12.5, 25 and 50 micrograms/rat) dose- and time-dependently inhibited brain ODC activity. While having no influence per se on pain threshold, DFMO significantly inhibited the analgesic activity of morphine (15 mg/kg i.p.), this effect being obtained when brain ODC activity was reduced by at least 80%. On the other hand, DFMO had no influence on number and affinity of brain opiate binding sites. Morphine per se neither modified whole brain ODC activity nor significantly affected the ODC inhibitory effect of DFMO. In more discrete brain areas (midbrain, brainstem) morphine actually increased ODC activity. The present results indicate that brain ODC/polyamines system may play a role in the analgesic activity of opioids, probably at a post-receptorial level or through a non-opiate receptor-linked mechanism.