Inhibition by adenosine analogs of opiate withdrawal effects.

The stable derivatives of adenosine, 2-chloroadenosine and N6-cyclohexyladenosine, with high affinity for the A1 (Ri) adenosine receptor, suppress the naloxone-precipitated withdrawal contracture of the opiate-dependent guinea-pig ileum in vitro. These adenosine derivatives also inhibit naloxone-precipitated jumping, diarrhea and weight-loss in morphine-dependent mice. This effect was not due to sedation, since (i) 2-chloroadenosine was effective at a non-sedative dose and (ii) sedative doses of chlordiazepoxide were ineffective.