A1 adenosine receptors in the rat prepinform cortex play an important role in the inhibition of bicuculline methiodide-induced convulsions. In the present study we evaluated manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the rat prepiriform cortex. Administration of exogenous adenosine afforded a dose-dependent protection (ED= 48.1±8.4 nmol) against bicuculline methiodide-induced seizures, and these anticonvulsant effects were significantly potentiated by treatment with an adenosine kinase inhibitor, 5’-amino-5’-deoxyadenosine; by the adenosine transport blockers, dilazep or nitrobenzylthioinosine 5’-monophosphate; and by an adenosine deaminase inhibitor, 2’-deoxycoformycin. When ad-ministered alone, 5’-amino-5’-deoxyadenosine, 5’-iodotuberci-din and dilazep were found to be highly efficacious as anticonvulsants with respective ED values of 2.6±0.8, 4.0±2.7 and

5.6±1.6 nmol. In contrast, 2’-deoxycoformycin was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the central nervous system. The adenosine antagonist, 8-(p-sulfophenyl) theophylline, increased markedly the severity of bicuculline methiodide-induced seizures. Moreover, reduction of extracellular adenosine formation by a focal injection of an ecto-5’-nucleotidase inhibitor, aj3-methyleneadenosine di-phosphate, produced generalized seizures (ED,= 37.3±22.7 nmol). Together the proconvulsant effect of an adenosine receptor antagonist and the convulsant action of an ecto-5’-nucleotidase inhibitor further support the role of endogenous adenosine as a tonically active antiepileptogenic substance in the rat prepiriform cortex.

Adenosine is an endogenous purine nucleoside which exerts characteristic inhibitory actions on neuronal firing rates, syn-aptic transmission and neurotransmitter release in the CNS (Phillis and Wu, 1981; Snyder, 1985). It has been shown that adenosine functions as a modulator, particularly within the cardiovascular and nervous system by acting on extracellularly directed adenosine receptors which are classified into at least two categories, termed A1 (R) and A2 (Rj)(van Calker et at., 1979; Londos et at., 1980). A1R and A2 adenosine receptors were characterized initially on the basis of their ability to either inhibit or activate the enzyme adenylyl cyclase, respectively. More recently A1R and A2 adenosine receptors have been distinguished with respect to their agonist pharmacological profiles. Both A1R-and A2 receptor-mediated effects are