A PYRROLOPYRIMIDINE WITH DEPRESSANT ACTIONS ON THE CENTRAL NERVOUS SYSTEM

¹ Department of Pharmacology, University of Kansas Medical Center, Kansas City, Kansas

BW 58-271, a pyrrolopynimidine, is a potent hypnotic agent as measured by the dose required to cause loss of righting reflex in mice. BW 58-271 is about 3 times as potent as hexobarbital in this test. As with many central nervous system (CNS) depressants, barbiturate anesthesia in rats is potentiated by BW 58-271. The compound possesses a local anesthetic action when applied to the isolated frog sciatic nerve, but is less potent than lidocaine. Intravenous doses of 4 mg/kg or more in anesthetized cats cause block of the spontaneous electrical activity of the electroencephalogram (EEG) lasting for several minutes. These periods in which no electrical activity is recorded are interspersed with bursts of high voltage waves. Evoked cortical activity as measured by the primary positive visual evoked potential is not blocked by 4 to 8 mg/kg of BW 58-271 i.v., but the latency of the waves is increased. In contrast to the primary positive evoked potential, later positive waves (up to 250 msec) are depressed more than negative deflections. The effects on latency of the primary waves and the depression or block of the late waves coincide with EEG suppression. These changes are not the result of hypotension, since comparable falls in blood pressure from tetraethylammonium chloride and spinal cord section do not cause similar EEG or evoked potential changes.