Propylene glycol as a drug solvent in pharmacologic studies

Pharmacologic activity of propylene glycol (PG) was evaluated, using several procedures commonly employed in drug screening. Acute pretreatment of mice with 2.08 g/kg of PG (equivalent to administration of 0.01 ml/g of a 20% solution) produced a significant elevation in initial clonic seizure threshold to iv infusion of pentylenetetrazol, not apparent with this dose when a single CD99 dose of convulsant was used. Parallel results were obtained at higher doses of PG vs. strychnine convulsions. Potentiation of hexobarbital sleeping time was observed at doses of PG below the TD50 of 5.77 g/kg. Higher doses decreased spontaneous motor activity. Subchronic administration of PG did not alter hexobarbital sleeping time subsequently determined, but did diminish diphenylhydantoin anti-MES (maximal electroshock seizure) activity. Thus, at cosolvent concentrations which might be employed in animal experiments, PG exhibits weak but significant CNS depressant activity as well as strychnine, pentylenetetrazol, tremorine, and oxotremorine antagonist action. There-fore, use of PG as an “inert” cosolvent in pharmacologic studies cannot be recommended when the ip route is employed.