Behavioral and cardiovascular effects of analogs of adenosine in cynomolgus monkeys

The behavioral and cardiovascular effects of six metabolically stable analogs of adenosine were studied in cynomolgus monkeys. Behavioral effects were determined in monkeys trained to respond under a 30-response fixed-ratio (FR) schedule of food presentation; cardiovascular effects were evaluated in a separate group of unanaesthetized monkeys seated at rest. Dose-effect curves for each drug were determined by administering cumulative doses i.v. during sequential components of the experimental session. All six analogs of adenosine produced dose-related decreases in FR responding with the following order of potency: 5'N-ethylcarboxamide adenosine (NECA) greater than 2-chloroadenosine (2-CA) greater than N6-R-phenylisopropyladenosine (R-PIA) greater than N6-cyclopentyladenosine (CPA) greater than N6-cyclohexyladenosine (CHA) greater than N6-S-phenylisopropyladenosine (S-PIA). In cardiovascular studies, all drugs except CPA produced dose-related decreases in mean blood pressure (MBP) with the following order of potency: NECA greater than 2-CA = R-PIA greater than CHA greater than S-PIA. CPA did not alter MBP at doses that decreased both FR responding and heart rate (HR). All drugs except NECA produced dose-related decreases in HR with the following order of potency: CPA greater than 2-CA greater than R-PIA greater than CHA greater than S-PIA. NECA increased HR at doses that decreased MPB and FR responding. Doses of caffeine that did not alter FR responding or cardiovascular function when given alone antagonized the behavioral effects of R-PIA, CHA, CPA and NECA. Caffeine also antagonized the effects of R-PIA, CHA and NECA on MBP and the effects of R-PIA and CPA on HR.(ABSTRACT TRUNCATED AT 250 WORDS)