Cited by 878Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Antipsychotic Drugs: Direct Correlation Between Clinical Potency and Presynaptic Action on Dopamine Neurons

Seeman, P., Lee, T.·1975·Science

DOI 10.1126/science.1145194

Open this paper in CoChat — free account

Abstract

Neuroleptic (antipsychotic) drugs inhibited the electrically stimulated release of [3 H]dopamine from rat striatal slices. The concentrations for 50 percent inhibition (ranging from 11.5 nanomolar for spiroperidol to 800 nanomolar for thioridazine) correlated closely with the average daily dosages of 25 neuroleptic drugs used clinically for schizophrenia. The correlation includes butyrophenones, phenothiazines, reserpine, pimozide, clozapine, and (+)-butaclamol. Clinically inactive isomers [trans-thiothixene,trans-flupenthixol, and (-)-butaclamol] required 20 to 1000 times higher concentrations than the active isomers to inhibit release. 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]GABA (γ-aminobutyric acid). The neuroleptic drugs may block the presynaptic coupling between impulse and neurosecretion.

Integrity signals

Registry

Crossref · 10.1126/science.1145194

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The Membrane Actions of Anesthetics and Tranquilizers
Seeman, P. M. (1972) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06931-5 · Cited by 2,241
Self-citation
Effect of Chlorpromazine or Haloperidol on Formation of 3‐Methoxytyramine and Normetanephrine in Mouse Brain
Carlsson, A., & Lindqvist, M. (1963) · Acta Pharmacologica et Toxicologica · doi:10.1111/j.1600-0773.1963.tb01730.x · Cited by 2,156
DOPAMINERGIC NEURONS: EFFECT OF ANTIPSYCHOTIC DRUGS AND AMPHETAMINE ON SINGLE CELL ACTIVITY
Bunney, B. S., Walters, J. R., Roth, R. H., & Aghajanian, G. K. (1973) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29539-8 · Cited by 1,283
Receptor activity and turnover of dopamine and noradrenaline after neuroleptics
Andén, N., Butcher, S. G., CORRODI, H., Fuxé, K., & Ungerstedt, U. (1970) · European Journal of Pharmacology · doi:10.1016/0014-2999(70)90006-3 · Cited by 1,026
Drugs, Neurotransmitters, and Schizophrenia
Snyder, S. H., Banerjee, S. P., Yamamura, H. I., & Greenberg, D. A. (1974) · Science · doi:10.1126/science.184.4143.1243 · Cited by 834
The significance of dopamine-receptor blockade for the mechanism of action of neuroleptic drugs.
Jm, V. R. (1966) · PubMed · Cited by 508
Dopamine-Sensitive Adenylate Cyclase in Mammalian Brain: A Possible Site of Action of Antipsychotic Drugs
Clement‐Cormier, Y. C., Kebabian, J. W., Petzold, G. L., & Greengard, P. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.4.1113 · Cited by 452
Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity
Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., & Atack, C. (1972) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1972.tb09104.x · Cited by 417
IS IT POSSIBLE TO PREDICT THE CLINICAL EFFECTS OF NEUROLEPTIC DRUGS (MAJOR TRANQUILLIZERS) FROM ANIMAL DATA?I. "NEUROLEPTIC ACTIVITY SPECTRA" FOR RATS.
Janssen, P. A., Cj, N., & Schellekens, K. H. L. (1965) · PubMed · Cited by 348
Antipsychotic drug actions: a clue to the neuropathology of schizophrenia?
Matthysse, S. (1973) · PubMed · Cited by 338

Flagged first, then by citations

Show all 35 references

Research works printed but not linked: 9

Aghajanian, G. K., Frontiers in Neurology and Neuroscience Research: 4 (1974).
FARNEBO, L. O., ACTA PHYSIOLOGICA SCANDINAVICA 371: 19 (1971).
FARNEBO, L. O., ACTA PHYSIOLOGICA SCANDINAVICA 371: 35 (1971).
Munkvad, I., The Neuroleptics. Modern Problems in Pharmacopsychiatrv 5: 44 (1970).
RITCHIE, J.M., ON ACTIVE STRUCTURE OF LOCAL ANESTHETICS, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 133: 241 (1961).
SEEMAN, P, FEDERATION PROCEEDINGS 33: 246 (1974).
SOTELO, C, ULTRASTRUCTURAL IDENTIFICATION OF NIGRAL DOPAMINERGIC CELLS IN RAT, JOURNAL DE PHARMACOLOGIE 5: 55 (1974).
STAWARZ, R.J., SIGNIFICANCE OF INCREASE OF HOMOVANILLIC-ACID (HVA) CAUSED BY ANTIPSYCHOTICS IN CORPUS STRIATUM AND LIMBIC FOREBRAIN, FEDERATION PROCEEDINGS 33: 246 (1974).
ZIVKOVIC, B, SPECIFIC ACTIVATION OF STRIATAL TYROSINE-HYDROXYLASE (TH) BY NEUROLEPTICS, FEDERATION PROCEEDINGS 33: 536 (1974).

Sorted by citations

Items 401–500 of 878

Effects of Methamphetamine Administration on Information Gathering during Probabilistic Reasoning in Healthy Humans
Ermakova, A. O., Ramachandra, P., Corlett, P. R., Fletcher, P. C., & Murray, G. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102683 · Cited by 26
A review of visual aftereffects in schizophrenia
Thakkar, K. N., Silverstein, S. M., & Brascamp, J. W. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.03.021 · Cited by 25
“These drugs achieve therapeutic effects by blocking dopamine (Seeman and Lee, 1975; Seeman et al., 1976), but also act on other neurotransmitter systems.”
Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia
Tardy, M., Huhn, M., Engel, R. R., & Leucht, S. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009230.pub2 · Cited by 27
Actions of a dopamine analogue and a neuroleptic at a neuroglandular synapse
House, C. R., & Ginsborg, B. L. (1976) · Nature · doi:10.1038/261332a0 · Cited by 26
Risks and Benefits of Bupropion Treatment in Schizophrenia
Englisch, S., Morgen, K., Meyer‐Lindenberg, A., & Zink, M. (2013) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e3182a8ea04 · Cited by 25
“This finding led to the early recognition that abnormal dopaminergic neurotransmission is central to psychosis in schizophrenia.(12) Specifically, psychosis has been linked to a “hyperdopaminergic” state.”
Background
Historical Overview: Introduction to the Dopamine Receptors
Seeman, P. M. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-333-6_1 · Cited by 25
“cies [ 12 ]; however, the antipsychotic concentrations required for this presynaptic action are much higher than those that inhibit [ 3 H]haloperidol binding to the D2 receptors (lower line )o r those”
BackgroundInfluentialSelf-citation
Interaction of haloperidol plasma level and antipsychotic effect in early phases of acute psychosis treatment
Giegling, I., Drago, A., Schäfer, M. K.-H., Möller, H., Rujescu, D., & Serretti, A. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.11.004 · Cited by 25
“Our result is consistent with some evidence retrieved from neuroimaging studies: it is well accepted that the therapeutic effect of antipsychotics, and their associated side effect profile, is based on their ability to bind D2 receptors (Creese et al., 1976; Seeman and Lee, 1975), and it is estimated that a D2 occupan…”
Prediction of h5-HT2A receptor antagonistic activity of arylindoles: Computational approach using topochemical descriptors
Dureja, H., & Madan, A. K. (2006) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2006.02.004 · Cited by 25
Neuroreceptor Imaging Studies in Schizophrenia
Frankle, W. G. (2007) · Harvard Review of Psychiatry · doi:10.1080/10673220701679812 · Cited by 25
Prolegomenon to the clinical prerequisite: Psychopharmacology and the classification of mental disorders
Ban, T. A. (1987) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(87)90019-4 · Cited by 25
Stereotyped Behavior and Stress
Valenstein, E. S. (1976) · Springer eBooks · doi:10.1007/978-1-4684-2238-2_7 · Cited by 25
The effect of neuroleptic drugs on drinking induced by central administration of angiotensin or carbachol
Sumners, C., Woodruff, G. N., Poat, J. A., & Munday, K. A. (1979) · Psychopharmacology · doi:10.1007/bf00426670 · Cited by 25
Behavioral evidence for dopaminergic supersensitivity following chronic treatment with methadone or chlorpromazine in the guinea pig
Eibergen, R. D., & Carlson, K. R. (1976) · Psychopharmacology · doi:10.1007/bf00423252 · Cited by 25
“For example, neuroleptics inhibit the release of dopamine (Seeman and Lee, 1975), a process which might contribute to the development of supersensitivity.”
Background
N-methyl-d-aspartate antagonists as drug models of schizophrenia: a surprising link to tobacco smoking
Domino, E. F., Mirzoyan, D., & Tsukada, H. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.05.024 · Cited by 24
Delayed onset hypothesis of antipsychotic action — a hypothesis tested and rejected
Agid, O., Kapur, S., Arenovich, T., & Zipursky, R. B. (2003) · Schizophrenia Research · doi:10.1016/s0920-9964(03)80242-6 · Cited by 24
Drugs and the developing central nervous system
Vernadakis, A. (1980) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(80)90043-1 · Cited by 24
Effects of acute and chronic systemic administration of some typical antipsychotic drugs on turnover of dopamine and potassium ion-induced release of dopamine in the striatum of the rat in vivo
Patterson, T. A., & Schenk, J. O. (1991) · Neuropharmacology · doi:10.1016/0028-3908(91)90107-m · Cited by 24
Multivariate Data Analysis in Structure—Activity Relationships
Lewi, P. J. (1980) · Elsevier eBooks · doi:10.1016/b978-0-12-060310-7.50013-4 · Cited by 24
Neuroleptic binding and their effects on the spontaneous and potassium-evoked release of 3H-dopamine from the striatum and of 3H-noradrenaline from the cerebral cortex
Arbilla, S., Briley, M., Dubocovich, M. L., & Langer, S. Z. (1978) · Life Sciences · doi:10.1016/0024-3205(78)90107-8 · Cited by 24
Low methylation rates of dopamine receptor D2 gene promoter sites in Japanese schizophrenia subjects
Yoshino, Y., Kawabe, K., Mori, T., Mori, Y., Yamazaki, K., Numata, S., Nakata, S., Yoshida, T., Iga, J., Ohmori, T., et al. (2016) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2016.1197424 · Cited by 23
“The dopamine hypothesis was proposed after observing the effect of neuroleptic drugs on SCZ patients (Seeman & Lee 1975; Seeman et al. 1976).”
Background
Effect of flupenthixol and butaclamol isomers on prolactin secretion in rats
Meltzer, H. Y., Paul, S. M., & Fang, V. S. (1977) · Psychopharmacology · doi:10.1007/bf00431737 · Cited by 23
Cholesterol and Ceramide Facilitate Membrane Fusion Mediated by the Fusion Peptide of the SARS-CoV-2 Spike Protein
Niort, K., Dancourt, J., Boedec, E., Dache, Z. A. A., Lavieu, G., & Tareste, D. C. (2023) · ACS Omega · doi:10.1021/acsomega.3c03610 · Cited by 22
PET translates neurophysiology into images: A review to stimulate a network between neuroimaging and basic research
Giovacchini, G., Squitieri, F., Esmaeilzadeh, M., Milano, A., Mansi, L., & Ciarmiello, A. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22451 · Cited by 22
“This hypothesis was initially formulated following clinical observations that all effective antipsychotic drugs provided some degree of D2 receptors blockade and that fact that dopamine agonists tend to JOURNAL OF CELLULAR PHYSIOLOGY exacerbate the symptoms of schizophrenia (Seeman and Lee, 1975).”
Background
Molecular imaging as a guide for the treatment of central nervous system disorders
Kim, E., Howes, O. D., & Kapur, S. (2013) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2013.15.3/ekim · Cited by 22
Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia
Neary, J. L., Perez, S. M., Peterson, K. R., Lodge, D. J., & Carless, M. A. (2017) · Genomics · doi:10.1016/j.ygeno.2017.03.004 · Cited by 23
Discovery of GlyT1 inhibitors with improved pharmacokinetic properties
Wolkenberg, S. E., Zhao, Z., Wisnoski, D. D., Leister, W., O'Brien, J. L., Lemaire, W., Williams, D. L., Jacobson, M. A., Sur, C., Kinney, G. G., et al. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.01.015 · Cited by 22
Dopamine and glutamate dysfunctions in schizophrenia: Role of the dopamine D3 receptor
Leriche, L., Díaz, J., & Sokoloff, P. (2004) · Neurotoxicity Research · doi:10.1007/bf03033298 · Cited by 22
“Carlsson's initial results and conclusions were later confirmed by numerous studies in vivo and in vitro utilizing both functional and biochemical studies in experimental animals (Anden et al., 1964; Anden et al., 1966; Carlsson et al., 1966; Anden et al., 1970; Nyback and Sedvall, 1970; Aghajanian and Bunney, 1973; S…”
Result
Cholinergic suppression: a postsynaptic mechanism of long-term associative learning.
Morielli, A. D., Matera, E. M., Kovac, M. P., Shrum, R. G., McCormack, K., & Davis, W. J. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.12.4556 · Cited by 22
Amphetamine effects on stimulus-elicited investigation in the mongolian gerbil
Cheal, M. (1978) · Physiology & Behavior · doi:10.1016/0031-9384(78)90084-7 · Cited by 22
Transient psychosis in women on clomiphene, bromocriptine, domperidone and related endocrine drugs
Seeman, M. V. (2015) · Gynecological Endocrinology · doi:10.3109/09513590.2015.1060957 · Cited by 22
Dysregulation of auditory neuroplasticity in schizophrenia
Voss, P., Thomas, M. E., Guercio, G. D., & de Villers‐Sidani, E. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.04.025 · Cited by 22
Analysis of methylation and -141C Ins/Del polymorphisms of the dopamine receptor D2 gene in patients with schizophrenia
Funahashi, Y., Yoshino, Y., Yamazaki, K., Ozaki, Y., Mori, Y., Mori, T., Ochi, S., Iga, J., & Ueno, S. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.06.001 · Cited by 21
Psychotherapeutic Drugs and Biogenic Amines Current Concepts and Therapeutic Implications
Potter, W. Z. (1984) · Drugs · doi:10.2165/00003495-198428020-00003 · Cited by 21
COMPARISON OF PIMOZIDE WITH HALOPERIDOL IN GILLES DE LA TOURETTE SYNDROME
Ross, M., & Moldofsky, H. (1977) · The Lancet · doi:10.1016/s0140-6736(77)91126-6 · Cited by 21
OBSERVATIONS CONCERNING NEUROTRANSMITTER INTERACTION IN SCHIZOPHRENIA
Lloyd, K. G. (1978) · Elsevier eBooks · doi:10.1016/b978-0-12-147850-6.50023-4 · Cited by 21
Cerebrospinal Fluid Studies in Schizophrenia
van Kammen, D. P., & Sternberg, D. E. (1980) · Springer eBooks · doi:10.1007/978-1-4684-1039-6_48 · Cited by 21
Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders
Aryutova, K., & Stoyanov, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179309 · Cited by 20
“This hypothesis is supported by the correlation between the action of antipsychotic drugs and their efficacy in blocking dopamine D2 receptors [36], as well as by the psychotic phenomena triggered by the dopamine agonists [37].”
Background
Relationship of frontal D2/3 binding potentials to cognition: a study of antipsychotic-naive schizophrenia patients
Fagerlund, B., Pinborg, L. H., Mortensen, E. L., Friberg, L., Baaré, W. F. C., Gade, A., Svarer, C., & Glenthoj, B. Y. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114571200003x · Cited by 20
The biochemical womb of schizophrenia: A review
Gaur, N., Gautam, S., Gaur, M. C., Sharma, P., Dadheech, G., & Mishra, S. (2008) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-008-0071-x · Cited by 19
“The classical “dopamine hypothesis of schizophrenia” postulates a hyperactivity of dopaminergic transmission at the dopamine D2 receptor in the mesencephalic projections to the limbic striatum especially in the etiology of positive symptoms (8-10).”
Background
A Manual Segmentation Tool for Three-Dimensional Neuron Datasets
Magliaro, C., Callara, A. L., Vanello, N., & Ahluwalia, A. D. (2017) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2017.00036 · Cited by 18
“…Billeci et al., 2013), the relationships between neuronal shape and function (Costa Lda et al., 2002; Brown et al., 2005; White, 2007) or the eﬀects of speciﬁc compounds on neuron geometry that could give useful information for designing new drugs (Seeman and Lee, 1975; Robinson and Kolb, 1999).”
Background
Haloperidol, a dopaminergic antagonist: Somatostatin-like inhibition of glucagon and insulin release from the isolated, perfused canine pancreas
Hermansen, K. (1978) · Diabetologia · doi:10.1007/bf03161000 · Cited by 20
“[13] who found that Haloperidol inhibits neurosecretion and that the inhibition of the neurosecretion could be elevated by high calcium concentrations.”
Background
Decreased [3H]spiperone binding in the anterior cingulate cortex of schizophrenia patients: an autoradiographic study
Zavitsanou, K., & Huang, X. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00533-4 · Cited by 20
Genetic association analysis of N‐methyl‐ d ‐aspartate receptor subunit geneGRIN2Band clinical response to clozapine
Taylor, D. L., Tiwari, A. K., Lieberman, J. A., Potkin, S. G., Meltzer, H. Y., Knight, J., Remington, G. J., Müller, D. J., & Kennedy, J. L. (2016) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2519 · Cited by 20
“Psychopharmacol Clin Exp 2016; 31: 121–134 DOI: 10.1002/hup weak affinity for DRD2 (Seeman and Lee, 1975; Creese et al., 1976), CLZ also has a high affinity for the serotonin-type 2A receptor (5-HT2A) (Meltzer et al., 1989) and a moderate affinity for the serotonin-type 1A receptor (5-HT1A) (Schotte et al., 1996), and…”
BackgroundInfluential
Time course of antipsychotic treatment response in schizophrenia: Results from a naturalistic study in 280 patients
Jäger, M., Riedel, M. J., Obermeier, M., Schennach-Wolff, R., Seemüller, F., Messer, T., Laux, G., Pfeiffer, H., Naber, D., Schmidt, L., et al. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2010.02.002 · Cited by 19
Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study
Oosterhof, C. A., Mansari, M. E., Bundgaard, C., & Blier, P. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv111 · Cited by 19
“Although D2 receptor antagonism effectively reduces positive symptoms in schizophrenia (Seeman and Lee, 1975; Rao and Remington, 2013), blockade of the D2-receptor–mediated signal might be undesirable for management of negative and/or cognitive symptoms.”
Background
Dopamine in psychiatry: a historical perspective
Foley, P. B. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-01987-0 · Cited by 19
Possible dose–side effect relationship of antipsychotic drugs: relevance to cognitive function in schizophrenia
Sumiyoshi, T. (2008) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.1.6.791 · Cited by 19
Optogenetic approaches for investigating neural pathways implicated in schizophrenia and related disorders
Cho, K. K. A., & Sohal, V. S. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu225 · Cited by 19
Dexamphetamine selectively increases 40 Hz auditory steady state response power to target and nontarget stimuli in healthy humans
Albrecht, M. A., Price, G. W., Lee, J. J., Iyyalol, R., & Martin-Iverson, M. T. (2012) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.110145 · Cited by 18
Transcriptomic signatures of schizophrenia revealed by dopamine perturbation in an ex vivo model
Duan, J., Göring, H. H. H., Sanders, A. R., Moy, W., Freda, J., Drigalenko, E. I., Kos, M. Z., S, D. H. B., Gejman, P. V., MGS, et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0216-5 · Cited by 19
Trifluoperazine versus low-potency first-generation antipsychotic drugs for schizophrenia
Tardy, M., Dold, M., Engel, R. R., & Leucht, S. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009396.pub2 · Cited by 19
l-Sulpiride in young and elderly negative schizophrenics: Clinical and pharmacokinetic variables
Mauri, M. C., Patrizia Leva, M., Coppola, T., & Altamura, C. A. (1994) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(94)90067-1 · Cited by 19
“Moreover, the ability of antipsychotic drugs to diminish positive symptoms has been correlated with their ability to bfock dopamine 02 receptors (Seeman and Lee 1975).”
Background
Neuroreceptor Imaging in Psychiatry: Theory and Applications
Frankle, W. G., Slifstein, M., Talbot, P. S., & Laruelle, M. A. (2005) · International review of neurobiology · doi:10.1016/s0074-7742(05)67011-0 · Cited by 19
“This hypothesis was essentially based on the observation that all eVective antipsychotic drugs provided at least some degree of D2 receptor blockade, an observation that is still true today (Creese et al., 1976; Seeman and Lee, 1975).”
Background
The Dopamine D2 Receptor
Civelli, O., Bunzow, J. R., Albert, P. R., Tol, H. H. M. V., & Grandy, D. K. (1992) · Birkhäuser Boston eBooks · doi:10.1007/978-1-4684-6772-7_7 · Cited by 19
Evoked release of endogenous amino acids from rat striatal slices and its modulation
Umeda, Y., & Sumi, T. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90198-2 · Cited by 19
The Enduring Centrality of Dopamine in the Pathophysiology of Schizophrenia
Bonoldi, I., & Howes, O. D. (2013) · Advances in pharmacology · doi:10.1016/b978-0-12-411512-5.00010-5 · Cited by 19
Translation of Central Nervous System Occupancy from Animal Models: Application of Pharmacokinetic/Pharmacodynamic Modeling
Melhem, M. R. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.199794 · Cited by 18
“The affinity of antipsychotic drugs for dopamine D2 receptors closely parallels their clinical potency (Seeman and Lee, 1975), and antipsychotic dopamine D2 receptor occupancy in vivo predicts both the clinical response of patients and the risk of side effects during antipsychotic treatment (Kapur…”
Background
Effects of ketamine on response properties of neurons in the superior paraolivary nucleus of the mouse
Felix, R. A., Kadner, A., & Berrebi, A. S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.11.027 · Cited by 18
“Acepromazine inhibits dopaminergic receptors (Feinberg and Snyder, 1975; Seeman and Lee 1975), and is recommended at a dosage of 1.”
BackgroundInfluential
Perceptual pathways to hallucinogenesis
Sheldon, A. D., Kafadar, E., Fisher, V., Greenwald, M. S., Aitken, F., Negreira, A. M., Woods, S. W., & Powers, A. R. (2022) · Schizophrenia Research · doi:10.1016/j.schres.2022.02.002 · Cited by 18
Brain uptake and distribution of the dopamine D3/D2 receptor partial agonist [11C]cariprazine: An in vivo positron emission tomography study in nonhuman primates
Tóth, M., Varrone, A., Steiger, C., Laszlovszky, I., Horváth, A., Kiss, B., Gyertyán, I., Adham, N., Halldin, C., & Gulyás, B. Z. (2012) · Synapse · doi:10.1002/syn.21631 · Cited by 18
Employing proteomics to unravel the molecular effects of antipsychotics and their role in schizophrenia
Cassoli, J. S., Guest, P. C., Santana, A. G., & Martins‐de‐Souza, D. (2015) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201500109 · Cited by 18
“Because of clinical success of chlorpromazine, other D2 antagonists were synthesized based on its chemical structure, such as haloperidol and fluphenazine [25, 29].”
Background
New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function
Uehara, T., Sumiyoshi, T., & Kurachi, M. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666151009120153 · Cited by 18
“Specifically, there is a linear relationship between clinical potencies of antipsychotic drugs and their affinity for D2 receptors in the brain [37-39].”
DNA Methylation Changes in Intron 1 of Triggering Receptor Expressed on Myeloid Cell 2 in Japanese Schizophrenia Subjects
Yoshino, Y., Ozaki, Y., Yamazaki, K., Sao, T., Mori, Y., Ochi, S., Iga, J., & Ueno, S. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00275 · Cited by 16
“…expressed on myeloid cell 2, TREM2, methylation rate, mRNA expression, pyrosequencing, susceptibility marker INTRODUCTION The dopamine hypothesis (Seeman and Lee, 1975) and the glutamate hypothesis (Hu et al., 2015) were proposed many years ago to explain the etiology of schizophrenia (SCZ).”
Background
Dyskinesias in monkeys: Interaction of methamphetamine with prior methadone treatment
Eibergen, R. D., & Carlson, K. R. (1976) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(76)90034-4 · Cited by 18
The Prolactin Response in Clinical Psychiatry
GRUEN, P. H. (1978) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)31815-6 · Cited by 18
Characterization of dopamine D2 receptor binding, expression and signaling in different brain regions of control and schizophrenia-model Wisket rats
Szűcs, E., Ducza, E., Büki, A., Kékesi, G., Benyhe, S., & Horváth, G. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147074 · Cited by 18
Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia
Bellon, A., Feuillet, V., Cortez-Resendiz, A., Mouaffak, F., Kong, L., Hong, L. E., Godoy, L. D., Jay, T. M., Hosmalin, A., & Krebs, M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01514-w · Cited by 19
Consciousness, (meta)cognition, and culture
Frith, C. (2023) · Quarterly Journal of Experimental Psychology · doi:10.1177/17470218231164502 · Cited by 20
“In the 1970s, it had been shown that there was a strong correlation between the clinical effectiveness of these drugs and their ability to block dopamine receptors (Seeman & Lee, 1975).”
Background
CSF dopamine is elevated in first-episode psychosis and associates to symptom severity and cognitive performance
Orhan, F., Goiny, M., Becklén, M., Mathé, L., Piehl, F., Schwieler, L., Fatouros‐Bergman, H., Farde, L., Červenka, S., Sellgren, C. M., et al. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2023.05.012 · Cited by 17
Association between functional and structural connectivity of the corticostriatal network in people with schizophrenia and unaffected first-degree relatives
Li, P., Jing, R., Zhao, R., Shi, L., Sun, H., Ding, Z., Lin, X., Lü, L., & Yong Fan, A. (2020) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.190015 · Cited by 17
Perphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia
Tardy, M., Huhn, M., Engel, R. R., & Leucht, S. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009369.pub2 · Cited by 17
Cognitive processing of facial affect: Connectionist model of deviations in schizophrenia.
Carter, J. R., & Neufeld, R. W. J. (2007) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.116.2.290 · Cited by 17
“The most common association is that schizophrenia symptoms are related to excess dopaminereceptor activity (Bartha et al., 1997; Kapur et al., 1998; Seeman & Lee, 1975).”
Background
Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides
Zhao, Z., O’Brien, J. A., Lemaire, W., Williams, D. L., Jacobson, M. A., Sur, C., Pettibone, D. J., Tiller, P. R., Smith, S., Hartman, G. D., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.08.131 · Cited by 17
Antipsychotic drugs and dopamine-mediated responses in Aplysia neurons
Heiss, W., Hoyer, J., & Thalhammer, G. (1976) · Journal of Neural Transmission · doi:10.1007/bf01256509 · Cited by 17
The influence of stimulus parameters on the potentiation of striatal dopamine release by metoclopramide: In vivo voltammetric data
Stamford, J. A., Kruk, Z. L., & Miller, J. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90206-2 · Cited by 17
Perlapine and dopamine metabolism: Prediction of antipsychotic efficacy
Wilk, S., & Stanley, M. (1977) · European Journal of Pharmacology · doi:10.1016/0014-2999(77)90372-7 · Cited by 17
Dopamine, Psychosis, and Symptom Fluctuation: A Narrative Review
Novak, G., & Seeman, M. (2022) · Healthcare · doi:10.3390/healthcare10091713 · Cited by 17
Reinforcing the membrane-mediated mechanism of action of the anti-tuberculosis candidate drug thioridazine with molecular simulations
Kopeć, W., & Khandelia, H. (2014) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-014-9737-z · Cited by 16
“Being an antipsychotic drug, THZ operates as an antagonist of transmembrane dopamine receptors [24], that are overexpressed by cancer stem cells of some cancers [25].”
Background
A 4-year dopamine transporter (DAT) imaging study in neuroleptic-naive first episode schizophrenia patients
Mané, A., Gallego, J., Lomeña, F., Mateos, J. J., Fernández-Egea, E., Horga, G., Cot, A., Pavı́a, J., Bernardo, M., & Parellada, E. (2011) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2011.03.004 · Cited by 15
“This idea was initially based on the correlation between therapeutic doses of antipsychotic drugs and their potency to block D2 receptors (Seeman and Lee, 1975) as well as the psychotogenic effects of dopamineenhancing drugs, such as amphetamine (Lieberman et al., 1987).”
Background
Striatal neurometabolite levels in patients with schizophrenia undergoing long-term antipsychotic treatment: A proton magnetic resonance spectroscopy and reliability study
Plitman, E., Chavez, S., Nakajima, S., Iwata, Y., Chung, J. K., Caravaggio, F., Kim, J. N., Alshehri, Y., Chakravarty, M. M., Luca, V. D., et al. (2018) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2018.01.004 · Cited by 16
“Schizophrenia is a disabling illness that is currently treated using antipsychotics, which exert their effect primarily through dopamine D2 receptor antagonism (Frangou, 2008; Seeman and Lee, 1975).”
Background
Positive association between cerebral grey matter metabolism and dopamine D 2 /D 3 receptor availability in healthy and schizophrenia subjects: An 18 F-fluorodeoxyglucose and 18 F-fallypride positron emission tomography study
Mitelman, S. A., Buchsbaum, M. S., Christian, B. T., Merrill, B., Buchsbaum, B. R., Mukherjee, J., & Lehrer, D. S. (2019) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2019.1671609 · Cited by 16
“…treatment trials with chlorpromazine (Delay and Deniker 1952) and demonstration of a parallel between dopamine receptor binding and therapeutic dosage of antipsychotics (Seeman and Lee 1975; see reviews by Howes and Kapur 2009; Brisch et al. 2014; Winton-Brown et al. 2014; Jauhar et al. 2017).”
Background
Neurotransmitter Theories of Schizophrenia
Matthysse, S., & Sugarman, J. (1978) · Springer eBooks · doi:10.1007/978-1-4613-4042-3_7 · Cited by 16
Effects of lesions in the ventral noradrenergic bundle on behavior and response to psychotropic drugs in rats
Jerlicz, M., Kostowski, W., Bidziński, A., & Hauptmann, M. (1978) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(78)90346-5 · Cited by 16
Focus on GABAA receptor function
Hautzel, H., Müller, H. W., & Nikolaus, S. (2014) · Nuklearmedizin - NuclearMedicine · doi:10.3413/nukmed-0647-14-03 · Cited by 15
“Among the neurotransmitters implicated in AD, MDD and SZ are • catecholamines (49, 50, 54), • serotonin (5-HT) (22, 23, 50), • glutamate (16, 33, 40) and • acetylcholine (28, 29, 39).”
Background
Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia.
Caravaggio, F., Hahn, M., Nakajima, S., Gerretsen, P., Remington, G., & Graff-Guerrero, A. (2015) · Medical Hypotheses · doi:10.1016/j.mehy.2015.06.011 · Cited by 17
Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade
Fell, M. J., Katner, J., Rasmussen, K., Nikolayev, A., Kuo, M., Nelson, D. L. G., Perry, K. W., & Svensson, K. A. (2012) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2012.00049 · Cited by 15
“Indeed, typical and atypical antipsychotics differ greatly in terms of their ability to interact with a number of dopaminergic (e.g., D2, D3, and D4; Seeman and Lee, 1975; Seeman et al., 1997) serotonergic (e.g., 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7; Roth et al., 1994; Bymaster et al., 1996), adrenergic/muscarinic…”
Elevated TREM2 mRNA expression in leukocytes in schizophrenia but not major depressive disorder
Yoshino, Y., Kawabe, K., Yamazaki, K., Watanabe, S., Numata, S., Mori, Y., Yoshida, T., Iga, J., Ohmori, T., & Ueno, S. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1560-3 · Cited by 15
Investigation of Schizophrenia with Human Induced Pluripotent Stem Cells
Powell, S. K., O’Shea, C. P., Shannon, S. R., Akbarian, S., & Brennand, K. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-45493-7_6 · Cited by 16
Ser-311-Cys Polymorphism of the Dopamine D2 Receptor Gene and Schizophrenia. An Analysis of Schizophrenic Patients in Fukuoka.
Harano, M. (1997) · The Kurume Medical Journal · doi:10.2739/kurumemedj.44.201 · Cited by 15
The effects of yohimbine and neuroleptics on apomorphine-induced pecking behaviour in the pigeon
Akbas, O., Verimer, T., Onur, R., & KAYAALP, S. (1984) · Neuropharmacology · doi:10.1016/0028-3908(84)90042-x · Cited by 15
Potential synergistic action of 19 schizophrenia risk genes in the thalamus
Richard, E. A., Khlestova, E., Nanu, R., & Lisman, J. E. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.09.008 · Cited by 15
“DRD2: The clinical effectiveness of antipsychotic drugs used in the treatment of SZ correlates with their affinity for dopamine receptors (Creese et al., 1996; Seeman and Lee, 1975).”
Background
The role of calmodulin on Ca2+-dependent K+ transport regulation in the human red cell
Álvarez, J., Garcı́a-Sancho, J., & Herreros, B. (1986) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(86)90494-3 · Cited by 15
Effects on striatal and mesolimbic dopamine systems of a new potential antipsychotic drug -mezilamine- with weak cataleptogenic properties
Uzan, A., Fur, G. L., Mitrani, N., Kabouche, M., & DONADIEU, A.-M. (1978) · Life Sciences · doi:10.1016/0024-3205(78)90314-4 · Cited by 15
Paradigm shift required for translational research on the brain
Yoon, J. H., Lee, D., Lee, C., Cho, E., Lee, S., Cazenave‐Gassiot, A., Kim, K., Chae, S., Dennis, E. A., & Suh, P. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01218-x · Cited by 14
“Then, it was discovered that these drugs bind to dopamine receptors 78 .”
Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function
Pauli, A., Prata, D. P., Mechelli, A., Picchioni, M., Fu, C. H. Y., Chaddock, C. A., Kane, F., Kalidindi, S., McDonald, C., Kravariti, E., et al. (2012) · Human Brain Mapping · doi:10.1002/hbm.22061 · Cited by 14
“Dopamine receptor agonists can induce positive psychotic symptoms in healthy individuals, and dopamine receptor antagonists reduce the severity of positive psychotic symptoms [Janowsky and Risch, 1979; Seeman and Lee, 1975].”
Background
Chronic hyperdopaminergic activity of schizophrenia is associated with increased ΔFosB levels and cdk-5 signaling in the nucleus accumbens
Cantrup, R., Sathanantham, K., Rushlow, W. J., & Rajakumar, N. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.07.027 · Cited by 18
“First, antipsychotics all possess D2 dopamine receptor antagonism and D2 dopamine receptor antagonism is essential for their clinical efficacy (Seeman and Lee, 1975; Creese et al., 1976; Sigmundson, 1994).”
Background
Phospholipase C-β1 Hypofunction in the Pathogenesis of Schizophrenia
Kim, S.-W., Cho, T., & Lee, S. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00159 · Cited by 14
“Neural mechanisms underlying schizophrenia symptoms in several brain areas have been explained by abnormalities in the dopaminergic (15, 16), serotonergic (17, 18), muscarinic (19–22), and glutamatergic signaling (23–25).”
Background
Contextual perception under active inference
Mirza, M. B., Cullen, M., Parr, T., Shergill, S. S., & Moran, R. (2021) · Scientific Reports · doi:10.1038/s41598-021-95510-9 · Cited by 14
Delivery Systems and Dosing for Antipsychotics
Rabin, C. R., & Siegel, S. J. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25761-2_11 · Cited by 14
“1) (Seeman et al. 1975; Seeman and Lee 1975; Seemen and Tallerico 1998).”
Real-Life Clinical Experience With Cariprazine: A Systematic Review of Case Studies
Csehi, R., Dombi, Z. B., Sebe, B., & Molnár, M. J. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.827744 · Cited by 14

Authors: Seeman, P., & Lee, T.
Affiliations: University of Toronto (CA)
ORCID: Seeman, P.
Lee, T.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1975-06-20
Volume: 188
Issue: 4194
Pages: 1217-1219
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1145194
OpenAlex: W2006122360
Cited by: 869
References: 35
Citations by year: 2026: 5 · 2025: 8 · 2024: 13 · 2023: 16 · 2022: 22 · 2021: 13 · 2020: 18 · 2019: 36 · 2018: 21 · 2017: 30 · 2016: 26 · 2015: 28 · 2014: 37 · 2013: 23 · 2012: 32
FWCI: 62.55
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: antipsychotic drugs, presynaptic dopamine release, striatum, spiperone, thioridazine, butyrophenones, phenothiazines, reserpine, pimozide, clozapine, butaclamol, stereoisomers, acetylcholine release, GABA release, schizophrenia
MeSH terms: Acetylcholine, Animals, Corpus Striatum, Dopamine, Dose-Response Relationship, Drug, Electric Stimulation, gamma-Aminobutyric Acid, Haloperidol, Humans, Male, Neurons, Neurosecretion, Schizophrenia, Tranquilizing Agents, Tritium, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Antipsychotic Drugs: Direct Correlation Between Clinical Potency and Presynaptic Action on Dopamine Neurons

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks