A Pharmacologic Study of Some Nucleosides and Nucleotides

Adenosine, adenosine-5′-phosphoric acid (AMP), adenosine-5′-triphosphate (ATP), guanosine-5′-triphosphate (GTP), uridine, uridine-5′-triphosphate (UTP), and cytidine diphosphate-5′-choline (CDPCh) were studied in vitro and in vivo. The intraventricular injection of high doses of adenosine, ATP, and methacholine into rats elicited clonic-tonic convulsions or an akinetic state, or both. Perfusion of frog hearts in situ with equimolar concentrations of the “high-energy” compounds, with the exception of ATP, failed to exert any positive inotropic effects, ATP did not potentiate the inotropic actions of (—)-adrenaline or (—)-noradrenaline. The cholinergic-like properties of adenosine and ATP were partially antagonised by concomitant perfusion with methylene blue, ATP, but not adenosine, obliterated transitorily, the cardio-toxicity of pilocarpine. The inhibition of the isolated clam heart by AMP and ATP qualitatively resembled the effects of acetylcholine (Ach). Antagonism of the cardio-depressant properties of AMP and ATP by benzoquinonium and 5-hydroxytryptamine (5-HT) also supports previous evidence that the adenyl compounds act similarly to the cholinergic mediator, ATP produced marked contractions and a tonotropic effect on the oestrogenised, isolated, quiescent rat uterus; these effects were destroyed by low concentrations of (—)-adrenaline and papaverine. Adenosine, AMP, and CDPCh in equimolarities elicited no response from this test preparation.