Further studies on the inhibition of adenosine uptake into rat brain synaptosomes by adenosine derivatives and methylxanthines.

Various adenosine derivatives, methylxanthines and other compounds were tested for their abilities to inhibit the rapid uptake of adenosine by rat cerebral cortical synaptosomes. Several pharmacologically potent derivatives of adenosine were weak inhibitors of uptake with IC20 values in excess of 10(-5) M. Derivatives in this category were adenosine-5'-N-ethylcarboxamide, adenosine-5'-cyclopropylcarboxamide, N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine, 1-methylisoguanosine, 2-phenylaminoadenosine and 5-iodotubercidin. Several methylxanthines were very weak inhibitors of adenosine uptake. These included pentoxifylline, n-hexyltheophylline, n-butyltheobromine, and isoamyltheobromine. HL 725, a pyrimido-isoquinoline with potent phosphodiesterase inhibitory activity, inhibited adenosine uptake with an IC20 of 2.0 X 10(-6) M. PK 11195, a putative ligand for the peripheral benzodiazepine binding site did not alter uptake at a concentration of 10(-4) M.