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.
PHARMACOLOGICAL ACTIVITY OF CB-103 IN HAEMATOLOGICAL MALIGNANCIES - AN ORAL PAN-NOTCH INHIBITOR WITH A NOVEL MODE OF ACTION
