Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs

  title={Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs},
  author={Ian Creese and David R. Burt and Solomon H. Snyder},
  pages={481 - 483}
Tritiated haloperidol and tritiated dopamine label postsynaptic dopamine receptors in mammalian brain. Clinical potencies of butyrophenones, phenothiazines, and related drugs correlate closely with their ability to inhibit tritiated haloperidol binding. These binding methods provide a simple in vitro means for evaluating new drugs as potential antischizophrenic agents. 

Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic, and histamine receptors to clinical potency.

The authors examined the potencies of 22 neuroleptic drugs competing for binding sites associated with dopamine, serotonin, alpha-adrenergic, and histamine receptors in brain membranes. They found

Neuroleptic Binding to Human Brain Receptors: Relation to Clinical Effects a

  • E. Richelson
  • Psychology, Biology
    Annals of the New York Academy of Sciences
  • 1988
The pharmacological effects of neuroleptics at receptors in brain and elsewhere in the body are likely responsible for therapeutic and certain adverse effects as well as some drug-drug interactions.

Dopamine receptors, neuroleptics, and schizophrenia.

  • S. Snyder
  • Psychology, Biology
    The American journal of psychiatry
  • 1981
The binding of 3H-butyrophenones to dopamine receptors can be used for a radioreceptor assay that detects blood levels of all clinically used neuroleptics and their pharmacologically active metabolites and may facilitate routine monitoring of blood levels.

Stereospecificity of interaction of neuroleptic drugs with neurotransmitters and correlation with clinical potency

If optical or geometrical isomers of a drug have markedly different clinical potencies, the most relevant biochemical effect should also exhibit isomeric specificity.

Dopaminergic D2 receptor binding of phenothiazine drugs and their metabolites

As a screening of their possible pharmacological activities, phenothiazine drug metabolites were examined for their binding affinities to dopamine D2 receptors in rat brain using radioligand binding techniques and the 7-hydroxy- and N-desmethyl metabolites had the highest binding affinity.

Receptor pharmacology of neuroleptics: relation to clinical effects.

  • E. Richelson
  • Psychology
    The Journal of clinical psychiatry
  • 1999
This article reviews the receptor pharmacology of neuroleptics, with a focus on newer drugs (e.g., risperidone, olanzapine, sertindole, quetiapines, and ziprasidone) in contrast to older compounds, based upon certain criteria, which are reviewed.

Striatal Dopamine Receptors: Dose-Dependent Occupation by, and Rapid Washout of, Orally Given Neuroleptics in Humans

Neuroleptic drugs are effective anti-psychotic agents, but the relationship between dosage and clinical response still is unclear and the usefulness of maintenance therapy is debated.

New drugs for the treatment of schizophrenic patients

  • W. Fleischhacker
  • Psychology, Medicine
    Acta psychiatrica Scandinavica. Supplementum
  • 1995
New strategies for treating schizophrenia include the development of dopamine antagonists with high selectivity for different subtypes of dopamine receptors, dopamine partial agonists, antagonists at different serotonin (5–hydroxytryptamine; 5–HT) receptor subtypes, drugs with mixed pharmacological profiles and drugs which modify transmission via amino acids or peptides in the brain.

The Interaction of Atypical Neuroleptics with Monoamine Receptor Subtypes

The modern „atypical neuroleptic“ must have beneficial effects on both the positive and negative symptoms of schizophrenia and the ability to improve cognitive function in patients that are otherwise resistant to drug intervention.



Chlorpromazine and dopamine: conformational similarities that correlate with the antischizophrenic activity of phenothiazine drugs.

  • A. HornS. Snyder
  • Chemistry, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1971
The ability of phenothiazine drugs to mimic the dopamine-like conformation correlates with their antischizophrenic efficacy and the importance of a substituent in ring a, a three-carbon side chain bearing the amino group, and a hetero atom between rings a and c is explained.

Brain receptors for antipsychotic drugs and dopamine: direct binding assays.

Various antipsychotic drugs inhibited this stereospecific component in both the dopamine and haloperidol assays, and these inhibitory potencies correlated with the clinical doses used for controlling schizophrenia.

Antipsychotic drugs and dopamine-stimulated adenylate cyclase prepared from corpus striatum of rat brain.

  • M. KarobathH. Leitich
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1974
Of 12 neuroleptic drugs with reported antipsychotic efficacy, all inhibit stimulation of adenylate cyclase by 40 muM dopamine at micromolar concentrations, and among 14 other structurally related drugs that are not clinically effective as antippsychotic agents, 12 were almost ineffective while two drugs were moderate inhibitors of dopamine-sensitive adenYLate cyclases.

Dopamine receptor binding in the corpus striatum of mammalian brain.

The relative potencies of phenothiazines as inhibitors of specific dopamine binding correlates with their clinical potencies and actions on the dopamine-sensitive adenylate cyclase.

Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons.

Compared to the inhibition of [3-H] dopamine release, much higher neuroleptic concentrations were needed to inhibit the electrically stimulated release of other neurotransmitters--[3- H] acetylcholine, [3,H-a1 (gamma-aminobutyric acid).

Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs.

The results raise the possibility that the therapeutic effects, as well as the extrapyramidal side effects, of these antipsychotic agents may be attributable, at least in part, to their ability to block the activation by dopamine of specific dopamine-sensitive adenylate cyclases in the human brain.

The Action of Neuroleptic Drugs on Dopamine-Stimulated Adenosine Cyclic 3',5'-Monophosphate Production in Rat Neostriatum and Limbic Forebrain

Neuroleptic drugs of various types were more potent inhibitors of dopamine-sensitive production of adenosine cyclic 39,59-monophosphate in homogenates of rat brain striatum than non-neuroleptic drugs

The conformation of neuroleptic drugs.

  • M. Koch
  • Psychology
    Molecular pharmacology
  • 1974
A study of the conformation of neuroleptic durgs by X-ray diffraction and simple conformational calculations has revealed some relationships among the relative arrangements of possible