Adenosine receptor antagonism accounts for the seizure-prolonging effects of aminophylline.

Abstract

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.

• Authors: M Dragunow
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 36 Issue 4 Pg. 751-5 (Aug 1990) ISSN: 0091-3057 [Print] United States
• PMID: 2217501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbolines
• Pyrazoles
• Pyrrolidinones
• Receptors, Purinergic
• Xanthines
• Picrotoxin
• methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
• Aminophylline
• N(6)-cyclohexyladenosine
• Flumazenil
• FG 7142
• 2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one
• Theophylline
• enprofylline
• 8-phenyltheophylline
• Rolipram
• Adenosine
• Diazepam

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Aminophylline (toxicity)
• Amygdala (drug effects, physiology)
• Animals
• Brain (anatomy & histology)
• Carbolines (pharmacology)
• Diazepam (antagonists & inhibitors)
• Flumazenil (pharmacology)
• Kindling, Neurologic
• Male
• Picrotoxin (pharmacology)
• Pyrazoles (pharmacology)
• Pyrrolidinones (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Purinergic (drug effects)
• Rolipram
• Seizures (chemically induced, physiopathology)
• Theophylline (analogs & derivatives, pharmacology)
• Xanthines (pharmacology)