Laghi Pasini F

Carnitines increase plasma levels of adenosine and ATP in humans.

In order to help to clarify the mode of action of carnitine derivatives, plasma levels of adenosine, ATP and inosine were evaluated following the infusion of 0.75, 0.50 and 0.25 mg/kg/min propionyl-L-carnitine (PLC) for 30 min in patients affected with peripheral arterial disease. Moreover, the effects of 0.75 mg/kg/min acetyl-L-carnitine (ALC) and L-carnitine (LC) were studied in the same conditions. Finally, the activity of 7.5 mg/kg/min PLC administered for 3 min was also evaluated. PLC and ALC produced a significant increase in plasma levels of adenosine and ATP, whereas LC induced less relevant changes. The administration of the compounds did not affect the adenosine/inosine ratio. Peak plasma levels of adenosine preceded in any case those of ATP. The possibility can be suggested that the pharmacological activity of PLC, ALC, and LC may be mediated, at least in part, by an interference with the endogenous purine system. Since these effects may be related to physiological mechanisms of tissue protection, new pharmacological perspectives for the compounds may arise.

Increase in plasma levels of adenosine and adenine nucleotides after intravenous infusion of buflomedil in humans

To clarify the mode of action of the vasoactive agent buflomedil, we evaluated plasma levels of adenosine and adenine nucleotides after intravenous (i.v.) infusion in humans of 50, 100, and 200 mg of the drug in 20 min. Buflomedil induced an increase of the same order of magnitude in plasma levels of adenosine and adenine nucleotides. Maximal adenosine increase (84%) was observed at the end of the infusion period, whereas peak plasma levels of ATP and ADP (69 and 55%, respectively) and of AMP (61%) were detected 10 and 5 min after discontinuation of infusion, respectively. Although the exact mode of action of buflomedil at the molecular level remains unclear, some indirect findings suggest that the increase in adenosine may be due to enhanced release rather than to inhibition of cell uptake. Because such activity of buflomedil consists of enhancement of physiologic mechanisms of vasodilation and tissue protection occurring in the course of ischemic events, new pharmacologic perspectives for the drug may arise.