Actions of Dinitrophenol

Abstract

Following the demonstration by C. Heymans 1 and others that α-dinitrophenol (1-2-4) produces fever in experimental animals, we have attempted to determine the cause of the rise of temperature, the effects on various functions, and its possible therapeutic applications.

Dinitrophenol produces fever in pigeons, rats, rabbits, cats, dogs, and man, in doses of 5 to 40 mg. per kilo, the exact dose depending on the species and route of administration. After subcutaneous or intramuscular injection, the temperature begins to rise in about 10 minutes and steadily increases until the maximum of up to 4°C. increase is reached, in from one-half to 4 hours. Then there may be a subsidence of the fever with complete recovery, or, if a fatal dose has been given, a sudden stoppage of respiration and circulation, and death. Rigor sets in at once.

Preceding the onset of the fever, and throughout the entire febrile period, there is a marked respiratory stimulation, including both the rate and depth, so the total ventilation increases up to 10 times the resting values. The respiratory stimulation may be prevented or diminished by large doses of morphine. Conversely, dinitrophenol increases the ventilation to better than the normal values after it has been decreased by toxic or fatal doses of morphine, chloral, alcohol or barbital. The stimulation compares favorably with that caused by caffeine. The improvement in respiration does not prevent death, if otherwise fatal doses of these hypnotics have been given; thus indicating that the respiratory depression per se is possibly not the primary cause of death from the hypnotics. During the period of maximum respiratory stimulation, there is little or no change in blood pressure and pulse rate, and the sugar, pH and CO₂-combining power of plasma are unaltered.