NGD 94-1 as an agonist at human recombinant dopamine D4.4 receptors expressed in HEK293 cells.
The atypical antipsychotic, clozapine has some selectivity for dopamine D4 receptors and is a silent antagonist at these receptors. NGD 94-1 (2-phenyl-4(5)-[4-(2-pyrimidinyl)-piperazin-1-yl-methyl]-imidazole ) is a highly selective dopamine D4 receptor ligand recently introduced as a putative antipsychotic mimicking the dopamine D4 receptor antagonist effects of clozapine. We show that NGD 94-1 is not silent. It behaved as an agonist in human embryonic kidney 293 cells expressing human recombinant dopamine D4.4 receptors. This questions the clinical use of NGD 94-1.
Gazi
L
L
Nervous System Therapeutic Area, Novartis Pharma Research, Novartis Pharma, Basel, Switzerland.
Sommer
B
B
Nozulak
J
J
Schoeffter
P
P
D002478:Cells, Cultured; D003024:Clozapine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050638:Receptors, Dopamine D4; D011994:Recombinant Proteins / Q000819:agonists
C493599:DRD4 protein, human; D018491:Dopamine Agonists; D007093:Imidazoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D011994:Recombinant Proteins; D050638:Receptors, Dopamine D4; C107692:NGD 94-1; D003024:Clozapine