Receptor mechanisms in antipsychotic drug action: focus on sigma receptors.
The principal antischizophrenic neuroleptic drugs in current clinical use act by blocking dopamine receptors, which mediate extrapyramidal side effects and tardive dyskinesia. As an alternative strategy, researchers have sought agents that do not influence dopamine receptors but whose behavioral effects in animals resemble those of neuroleptics. Some promising "new generation" candidate drugs have shown beneficial effects in schizophrenic patients in early clinical trials. These new agents share a selective, high affinity for sigma receptors, sites where psychotomimetic opiates act. A systematic screen for drugs that block sigma receptors may provide a valuable strategy in identifying novel antischizophrenic agents and in clarifying the pathophysiology of psychosis.
Snyder
S H
SH
Department of Neuroscience, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Largent
B L
BL
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D015195:Drug Design; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D017478:Receptors, Phencyclidine; D011985:Receptors, Serotonin / Q000187:drug effects; D017480:Receptors, sigma; D017330:Remoxipride; D012559:Schizophrenia / Q000188:drug therapy; D013141:Spiro Compounds / Q000494:pharmacology
D014150:Antipsychotic Agents; D001549:Benzamides; D002227:Carbazoles; D002243:Carbolines; D007546:Isoquinolines; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D011985:Receptors, Serotonin; D017480:Receptors, sigma; D013141:Spiro Compounds; D017330:Remoxipride; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C042709:tiospirone; C069280:gevotroline; C051009:HR 375; C048478:MJ 13980-1; C034931:rimcazole