Adenosine analogs and sleep in rats.

The effects of N6-L-(phenylisopropyl)adenosine, cyclohexyladenosine and adenosine-5'-N-ethylcarboxamide on sleep were examined in rats. These effects consist of 1) increased slow-wave sleep2 from 6.6 to 45.7%, in all doses used for cyclohexyladenosine and adenosine-5'-N-ethylcarboxamide and for 0.1 and 0.3 mumol/kg of N6-L-(phenylisopropyl)adenosine and 2) increased values for rapid-eye-movement-sleep, amounting to 56.2 and 51.6% for 0.1 mumol/kg of cyclohexyl-adenosine and 0.3 mumol/kg of N6-L-(phenylisopropyl)adenosine, respectively. Slow-wave sleep1 decreased but values for wakefulness and total sleep were unchanged for 0.03, 0.1 and 0.3-mumol/kg doses of the drugs. Only 0.9-mumol/kg dose of cyclohexyladenosine and N6-L-(phenylisopropyl)adenosine increased wakefulness and decreased total sleep, whereas the same dose of adenosine-5'-N-ethylcarboxamide increased total sleep during the 0- to 3-hr time interval. All three agents reduced rapid-eye-movement sleep at the 0.9-mumol/kg dose. The results indicate that the effect on sleep of all three adenosine analogs was obtained with nanomolar doses of the drugs and that it diminished or disappeared when the drug dose reached micromolar range (0.9 mumol/kg). It appears, therefore, that activation of A1 rather than A2 receptors contributed to the sleep effects of the drugs because adenosine and adenosine analogs activate A1 receptors in nanomolar quantities whereas activation of A2 receptors requires micromolar concentration of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)