ACUTE TOXICITY OF ADENOSINE 3', 5'-CYCLIC MONOPHOSPHATE

Abstract

Acute toxicity of Na-adenosine 3', 5'-cyclic monophosphate (Na-cAMP) was studied in mice. LD50 values (in g/kg) in males (m.) and females (f.) by three routes were as follows : p. o. : m. 14.3, f. 15.2 ; i. p. : m. 1.14, f. 0.395 ; i. v. : m. 1.57, f. 0.645. After a depression following the Na-cAMP administration (i. p. and i.v.) wore off, a delayed, progressive severe ataxia (just like a curare-induced ataxia) was noted 10-30 hr after the administration especially in females. If the ataxia once appeared, animals died in 2-3 hr without exception, seemingly from respiratory paralysis. The females given with highest doses and most of males died earlier in an extreme depression. In the ataxic animals, the twitch tension development of the hind limb induced by sciatic nerve stimulationin in situ was strongly suppressed as compared with that induced by direct stimulation. On the basis of the results and also of those of some electrophysiological studies in vitro, it is suggested that some disturbance of the motor nerve terminals may be a main cause of the ataxia. The question whether this ataxia is the primary toxic effect of cAMP or a secondary effect is now under investigation.