Hypothermia as a mechanism for drug-induced resistance to hypoxia.

A linear regression line relating the logarithm of survival time in a standard hypoxia survival test (4.6% oxygen) with hypothermia was obtained upon cooling mice by exposure to either a graded hypoxia or a cold environment. When S/BT values (log minutes survival versus body temperature) of drug-treated animals were compared with this regression line, values for many drugs lay on the line, indicating that their effects upon hypoxic survival were no greater than those expected from the concomitant hypothermia. Among the drugs whose anti-hypoxia effects were explained by their production of hypothermia were adenosine, diazepam, diphenylhydantoin, pentobarbital and physostigmine. The anti-hypoxia activity of each drug had been reported previously by other investigators and ascribed to numerous mechanisms. The present observations relating hypothermia with increased survival in hypoxia provide a rationale for the protective effect of the above drugs in animals suddenly exposed to lethal hypoxia.

N-o-Methoxyphenylpiperazine: a simple blocker of dopaminergic receptors in the brain.

N-o-Methoxyphenylpiperazine (MPP) is a moderately effective in vivo blocker of dopaminergic receptors. Its ability to increase the concentration of rat brain homovanillic acid (HVA) and the resulting time course for HVA were similar to the actions of clozapine. The increased concentration of HVA did not result from decreased outflow from brain because HVA also rapidly decreased after a subsequent injection of pargyline. MPP blocked the circling behaviour caused by apomorphine in mice with a unilateral striatal lesion, and MPP and apomorphine reciprocally blocked the occurrence of stereotypy and increased HVA in rats. Diazepam partially prevented the MPP-induced elevation of HVA. Thus, both biochemical and pharmacological evidence indicate the dopaminergic blocking action of MPP.