n(6)-cyclohexyladenosine and methyl-6-7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate

The anticonvulsant actions of the adenosine receptor agonists, 1-phenylisopropyladenosine, 2-chloroadenosine and cyclohexyl-adenosine, against DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate)-induced seizures in mice were studied with an infusion technique. 2-Chloroadenosine and cyclohexyladenosine were active at 1 mg/kg whereas 1-phenyl-isopropyladenosine was active at 0.03 mg/kg given i.p. At 10 mg/kg, 1-phenylisopropyladenosine was only weakly active against pentylenetetrazol-induced seizures and not active against bicuculline-induced seizures. The selective effect of 1-phenylisopropyladenosine against DMCM-induced seizures suggests that adenosine receptor agonists may allosterically counteract the negative modulating effect of DMCM on GABA coupling to the chloride channel. This indicates that adenosine receptors may have a physiological function within the GABA/benzodiazepine receptor complex in the brain.

Topics: 2-Chloroadenosine; Adenosine; Animals; Anticonvulsants; Bicuculline; Carbolines; Convulsants; Female; Mice; Pentylenetetrazole; Phenylisopropyladenosine; Receptors, Purinergic; Seizures; Theophylline

The mechanism of action of aminophylline in prolonging seizures was tested in amygdala-kindled rats. Aminophylline prolonged the afterdischarge duration of kindled seizures. This seizure-prolonging action of aminophylline was strongly antagonized by the adenosine A1 agonist cyclohexyladenosine and partially antagonized by the benzodiazepine partial agonist RO 15-1788. However, the specific benzodiazepine antagonist CGS 8216 did not affect the seizure-prolonging action of aminophylline. Also, the potent anticonvulsant effect of diazepam on kindled seizures, which was completely antagonized by CGS 8216, was unaffected by aminophylline. Furthermore, a range of benzodiazepine inverse agonists, GABA antagonists, phosphodiesterase inhibitors and xanthines did not prolong afterdischarge durations. These results demonstrate that the seizure-prolonging action of aminophylline is due to block of A1 adenosine receptors since it is prevented by adenosine A1 agonists.

Topics: Adenosine; Aminophylline; Amygdala; Animals; Brain; Carbolines; Diazepam; Flumazenil; Kindling, Neurologic; Male; Picrotoxin; Pyrazoles; Pyrrolidinones; Rats; Rats, Inbred Strains; Receptors, Purinergic; Rolipram; Seizures; Theophylline; Xanthines