Heat transfer by evaporation determines the effect of nasal phenazepam on thermal stress in rats

Introduction. Thermal stress is an increase in body temperature due to the predominance of heat received from outside or released during metabolism over heat losses by the body. Heat production can be regulated using benzodiazepines in doses unattainable with a single intramuscular injection of their officinal preparations. In this study, this limitation is overcome using a prototype of the Phenazepam nasal spray (PNS) preparation, containing 170 mg of phenazepam in 1 mL of a non-aqueous solution. Objective . Experimental assessment of the PNS effect on the metabolic rate and thermal balance in thermal stress. Materials and methods . The effect of a single 10 μL PNS intranasal instillation on the external respiration intensity, oxygen consumption, as well as 10 μL PNS intranasal instillations at 0.5 h intervals on the dynamics of rectal temperature, body weight, and lethality in rats at an air temperature of 40 °C was studied. Results . PNS instillations reduced oxygen consumption by an amount sufficient to decrease body temperature by 0.3 °C in 0.5 h. PNS administration declined the rate of body temperature rise when placing rats in restrainers at an air temperature of 40 °C; however, PNS administration accelerated body temperature rise and increased lethality when placing rats in cages. Due to PNS, moisture loss by rats in cages decreased, judged by the dynamics of body weight. Conclusions. The study confirmed the prospects of PNS as a pharmacotherapy for heat stroke at a high relative humidity, exposure to insulating skin protectors, or with immersion hyperthermia. The possibility of the aggravating effect of PNS on human thermal stress in the absence of physical obstacles to heat transfer by evaporation requires additional verification.