Dose-response effects of 8-cyclopropyltheophylline on sleep and wakefulness in rats

The dose-response effects of the substituted xanthine 8-cyclopropyltheophylline (CPRT) on sleep and wakefulness (W) after intraperitoneal administration to rats were examined by means of simultaneous electroencephalographic (EEG) and electromyographic (EMG) recordings. Doses of 20 and 40 mg/kg CPRT increased W and decreased slow wave sleep (SWS) in rats, indicating CNS stimulant effects. The greatest CNS stimulation was produced by the lowest (20 mg/kg) dose of CPRT examined, which also increased the latency to SWS. In addition, the 20 mg/kg dose of CPRT also significantly decreased the amount of total sleep (TS), as compared to the vehicle group, during all time periods examined. In contrast, the 80 mg/kg dose of CPRT decreased W and increased both SWS and TS. However, this apparent hypnotic effect of the 80 mg/kg CPRT may be due to toxicity, since 80% of rats treated with this dose of the drug died within 48 h of injection.