ACEA-1021, A GLYCINE SITE ANTAGONIST WITH MINOR PSYCHOTOMIMETIC AND AMNESTIC EFFECTS IN RATS

Antagonists of the allosteric glycine site of the NMDA receptor comple x have been suggested to be beneficial in the treatment of neurodegene rative disorders. However, unwanted side effects like psychomotor stim ulation and amnesia must be expected. ACEA 1021 (5-nitro-6,7-dichloro- 1,4-dihydroquioxaline-2,3 dione) is one of the first high-selective gl ycine site antagonists which passes the blood-brain barrier and which has promising anticonvulsive and neuroprotective properties. In the pr esent study the effects of ACEA 1021 (5, 7.5, 8, 10, 15 and 20 mg/kg i .p.) on sniffing stereotypy, locomotor activity, prepulse inhibition o f the acoustic startle response, the anti-cataleptic properties and sp atial learning were tested. Only 7.5 mg/kg ACEA 1021 induced a sniffin g stereotypy which was antagonized by the partial glycine site agonist D-cycloserine (D-4-amino-3-isoxazolidinone). ACEA 1021 had neither an effect on motor behavior measured in the open field nor on the acoust ic startle response in the prepulse inhibition paradigm nor on the acq uisition of spatial learning in the 8-arm-radial maze. Anti-cataleptic properties of ACEA 1021 in dopamine D-2 (haloperidol hydoxy-4-p-chlor ophenyl-piperidino)-butyrophenon)) or D-1 (SCH 23390 ethyl-1-phenyl-2, 3,4,5-tetrahydro-1H-3-benzazepine hydrochloride)) receptor antagonist- pretreated rats were only minor. Thus, ACEA 1021 is a glycine site ant agonist with minimal psychotomimetic side effects and with no amnesia properties. However, it has only minor anti-parkinsonian effects. (C) 1997 Elsevier Science B.V.