Antipsychotic drug doses and neuroleptic/dopamine receptors

  title={Antipsychotic drug doses and neuroleptic/dopamine receptors},
  author={Phillip Seeman and T. Lee and M Chau-Wong and K Wong},
ANTIPSYCHOTIC drugs, or neuroleptics, are thought to act by blocking dopamine receptors in the nervous system1–4. Recent direct evidence, based on stereospecific binding assays, supports this hypothesis of antipsychotic drug action5–9. As only a few antipsychotic drugs had been tested for their effects on the binding of haloperidol5–8, the question remained whether all antipsychotic drugs, regardless of chemical structure, would block the stereospecific binding of haloperidol. We report here… 
Dopamine receptors, neuroleptics, and schizophrenia.
  • S. Snyder
  • Medicine
    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.
Antipsychotic drug mechanisms and neurotransmitter systems in schizophrenia
  • G. Reynolds
  • Psychology, Medicine
    Acta psychiatrica Scandinavica. Supplementum
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The dopamine hypothesis of schizophrenia has been central to the understanding of the mechanism of action of the antipsychotic drugs and effects at other receptors are reported to be of value in minimizing extrapyramidal syndromes as well as in enhancing response either directly or by diminishing negative symptoms.
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
Inverse agonism of the antipsychotic drugs at the D2 dopamine receptor
The antipsychotic drugs had been assumed to act as antagonists at D2 dopamine receptors but recently these drugs have been shown to possess inverse agonist properties at this receptor. Inverse
Serotonin in antipsychotic drugs action
  • D. Amato
  • Psychology, Medicine
    Behavioural Brain Research
  • 2015
The present work will overview the antipsychotic drugs effects on serotonin levels as measured with microdialysis in the rat brain and provide an exhaustive reference for who is interested, at any levels, in antipsychotics effects on cortical and subcortical serotonin output.
Dopamine Receptors and Antipsychotic Drugs in Health and Disease
In this article, the history of the discovery of dopamine receptors is given, from the original observation that antipsychotic drugs elicit parkinsonism to the final discovery of the dopamine D2
Clozapine: Mechanism of Action in Relation to its Clinical Advantages
Clozapine, a dibenzodiazepine, is the prototype of an atypical antipsychotic drug that produces weak catalepsy in rodents, minimal extrapyramidal side effects (EPS) at clinically effective doses, and minimal plasma prolactin (PRL) elevations in humans.
Antiparkinsonian drug doses and neuroleptic receptors
The clinical potency of 3 drugs, apomorphine, N-propylnorapomorphine, and bromocryptine, have been found to be closely correlated to their potencies in competing for3H-haloperidol and3H-spiroperidol
The effect of chronic neuroleptic administration on cerebral dopamine receptor function.
It has been discovered that chronic administration of neuroleptic drugs may have different effects on cerebral dopamine systems, and initial antagonism of dopamine mediated behaviour, such as stereotypy, disappears and may be replaced by supersensitivity to dopamine agonists.
Antipsychotic drugs, dopamine receptors, and schizophrenia
  • P. Seeman
  • Chemistry
    Clinical Neuroscience Research
  • 2001
Abstract The clinical potencies of antipsychotic drugs are directly related to their affinities for the dopamine D2 receptor. In addition, the concentrations of antipsychotic drugs (given at


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: 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 receptor blockade and the neuroleptics, a crystallographic study
Further evidence is presented in support of the theory that the neuroleptics are able to block dopamine receptors because of a conformational complementarity between certain portions of these drugs and dopamine.
Dopamine receptor binding: differentiation of agonist and antagonist states with 3H-dopamine and 3H-haloperidol.
3H-Dopamine and 3H-haloperidol bind with high affinity and selectivity to synaptic dopamine receptors in membrane preparations of the calf caudate, and the rank-order of phenothiazines and related agents as well as catecholamines in displacing both dopamine and haloperidl binding closely parallels their pharmacological potencies and affinities for the dopamine-sensitive adenylate cyclase.
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.
The nerve impulse-blocking actions of tranquilizers and the binding of neuroleptics to synaptosome membranes.
It is suggested that presynaptic blockade of coupling (between impulse and dopamine release) may play a role in the antipsychotic and extrapyramidal actions of neuroleptics.
Physiologic and clinical effects of chlorpromazine and their relationship to plasma level
Plasma levels and clinical improvement were weakly related during the first 2 weeks of treatment only; clinical improvement correlated with palmar skin conductance (sweating) and with some latencies of the electroencephalographic‐evoked response.
Dopamine receptors in the brain.
An early clinical trial of lenperone (AHR 2277), a butyrophenone, in chronic schizophrenia.