NMDA receptor antagonists acting at the glycineB site in rat models for antipsychotic-like activity.
Several partial agonist and full antagonists acting at the glycine site of the NMDA receptors were tested for potential antipsychotic-like properties in rats. As models, amphetamine- and phencyclidine (PCP)-induced locomotor activation in the open field and PCP-induced impairment of prepulse inhibition of the acoustic startle response were employed. In the open field test, partial agonists, D-cycloserine failed to show any effect, aminocyclopropane carboxylic acid (ACPC) enhanced the action of PCP (but not that of amphetamine) and R(+)HA-966 attenuated the locomotor activation produced by both amphetamine and PCP. Both full glycineB antagonists, L-701,324 and MRZ 2/576 attenuated the action of amphetamine and PCP but at the doses that also produce transient behavioural inhibition in naive animals. A competitive NMDA receptor antagonist CGP 39551 was ineffective. In the prepulse inhibition test neither L-701,324 nor MRZ 2/576 changed sensorimotor gating in naive animals nor attenuated the disrupting effects of PCP. The present data do not support antipsychotic profile of glycineB full antagonists. However, psychotomimetic potential of glycineB antagonists seems to be low.
Karcz-Kubicha
M
M
Department of Pharmacological Research, Merz + Co., Frankfurt/Main, Federal Republic of Germany.
Wedzony
K
K
Zajaczkowski
W
W
Danysz
W
W
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects
D000963:Antimetabolites; D014150:Antipsychotic Agents; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; C112266:MRZ 2-576; D010793:Phthalazines; D011760:Pyrrolidinones; D015363:Quinolones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D003515:Cycloleucine; C064540:CGP 39551; C065594:cispentacin; D015763:2-Amino-5-phosphonovalerate; D003523:Cycloserine; D000661:Amphetamine; C001369:1-hydroxy-3-amino-2-pyrrolidone; C094635:L 701324; D010622:Phencyclidine; D005998:Glycine