EFFECT OF EPINEPHRINE AND NOREPINEPHRINE ON EXCITABILITY OF CENTRAL NERVOUS SYSTEM OF MICE

¹ Departments of Pharmacology, University of Utah College of Pharmacy and College of Medicine, Salt Lake City, Utah

The relative toxicity of epinephrine and norepinephrine and their effects on brain excitability were determined in mice. In addition, the effects of these agents on blood pH and acid-base balance were studied. Epinephrine appears to be 4 to 8 times more toxic than norepinephrine. Both drugs exerted a non-monotonic effect on pentylenetetrazol seizure threshold (PST). Small nontoxic doses of both catecholamines elevated PST and large toxic doses lowered this threshold. Epinephrine had a similar non-monotonic effect on electroshock seizure threshold (EST). On the other hand, small nontoxic doses of norepinephrine had no significant effect on EST, whereas large toxic doses lowered EST. Within 30 seconds after their intravenous injection, both catecholamines decreased blood pH and induced a metabolic acidosis accompanied by some respiratory acidosis; but these metabolic alterations were causally unrelated to changes in brain excitability. It is suggested that epinephrine and norepinephrine act directly on the CNS to alter brain excitability.