Adenosine A1 and A2 receptor agonists significantly prevent the electroencephalographic effects induced by MK-801 in rats.
Both N6-cyclopentyladenosine (CPA, adenosine A1 receptor agonist) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido-adenosi ne (CGS 21680, adenosine A2 receptor agonist) inhibited the electroencephalographic (EEG) effects induced by the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)cyclohepten-5,10-imine maleate (MK-801) in rats. While the inhibitory effects of CPA were evident at doses (0.1 and 0.5 mg/kg i.p.) devoid of intrinsic behavioral effects, CGS 21680 was effective only when administered at depressant doses (2 mg/kg i.p.). Since the effects induced by NMDA receptor antagonists may be regarded as a model of psychosis, these results suggest a possible role of adenosine receptor agonists as antipsychotics.
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Pharmacology Department, Istituto Superiore di Sanità, Rome, Italy.
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004569:Electroencephalography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D011605:Psychoses, Substance-Induced; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000959:Antihypertensive Agents; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D016194:Receptors, N-Methyl-D-Aspartate; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D016291:Dizocilpine Maleate; D000241:Adenosine