Prominent publications by Philip Seeman

KOL Index score: 17483

This review addresses two questions. First, why does clozapine apparently occupy low levels of dopamine D2 receptors in patients, in contrast to all other antipsychotic drugs which occupy 70–80% of brain dopamine D2 receptors? Second, what is the receptor basis of action of antipsychotic drugs which elicit low levels of Parkinsonism? Antipsychotic doses of clozapine occupy between 0% and 50% of D2 receptors, as measured in patients by a variety of radioligands. It has recently been ...

Also Ranks for: Antipsychotic Drugs |  dopamine receptors |  human striatum |  receptor antagonists |  radioligand occupancy
KOL Index score: 16128

Repeated injections of the D2/D3 dopamine agonist, quinpirole, induce locomotor sensitization and compulsive checking behavior in rats, a phenomenon that may constitute an animal model of obsessive- compulsive disorder (OCD). Considering that the co-joint treatment with quinpirole and the kappa opioid receptor agonist U69593 potentiates locomotor sensitization to quinpirole, the present study examined whether such co-stimulation of kappa and dopamine receptors also enhances compulsive ...

Also Ranks for: Compulsive Checking |  quinpirole sensitization |  dopamine receptors |  opioid receptor |  animal model
KOL Index score: 15255

Using 32P-labelled oligonucleotides derived from the coding regions of dopamine D1, D2 and D3 receptor mRNAs we localized cells containing transcripts for these receptors in the human (hD1, hD2) and rat brain (rD1, rD2, rD3). Dopamine D1 receptor mRNA was detected at high levels in neurons of the caudate and putamen as well as in the nucleus accumbens in both human and rat brain. In the rat brain D1 receptor mRNA was also abundant in the olfactory tubercles and several thalamic nuclei. ...

Also Ranks for: Dopamine D1 |  d3 receptor |  rat brain |  substantia nigra |  ventral tegmental area
KOL Index score: 13772

Ketamine and PCP are commonly used as selective NMDA receptor antagonists to model the putative hypoglutamate state of schizophrenia and to test new antipsychotics. Recent findings question the NMDA receptor selectivity of these agents. To examine this further, we measured the affinity of ketamine and PCP for the high-affinity states of the dopamine D2 and serotonin 5-HT2 receptor and found that ketamine shows very similar affinity at the NMDA receptor and D2 sites with a slightly lower ...

Also Ranks for: Nmda Receptor |  ketamine pcp |  serotonin 5 |  direct effects |  models schizophrenia
KOL Index score: 13631

BACKGROUND: Although the principal brain target that all antipsychotic drugs attach to is the dopamine D2 receptor, traditional or typical antipsychotics, by attaching to it, induce extrapyramidal signs and symptoms (EPS). They also, by binding to the D2 receptor, elevate serum prolactin. Atypical antipsychotics given in dosages within the clinically effective range do not bring about these adverse clinical effects. To understand how these drugs work, it is important to examine the ...

Also Ranks for: Atypical Antipsychotic |  dopamine receptors |  clozapine quetiapine |  dissociation constants |  serotonin 5
KOL Index score: 13280

Dopamine D1 receptors were solubilized from canine and bovine striatal membranes with the detergent digitonin. The receptors retained the pharmacological characteristics of membrane-bound D1 receptors, as assessed by the binding of the selective antagonist [3H]SCH 23390. The binding of [3H]SCH 23390 to solubilized receptor preparations was specific, saturable, and reversible, with a dissociation constant of 5 nM. Dopaminergic antagonists and agonists inhibited [3H]SCH 23390 binding in a ...

Also Ranks for: D1 Receptors |  guanine nucleotide |  dopamine receptor |  3hsch 23390 |  rank order
KOL Index score: 12319

The purpose of this study was to determine whether dopamine D4 receptors could be detected in the human brain striatum by means of an indirect ligand-binding method, because no dopamine D4 receptor-selective ligand presently exists. The antipsychotic clozapine is more selective for the dopamine D4 receptor than for other dopamine receptors. Although most antipsychotic drugs act in the striatum to elicit Parkinson-like side-effects, clozapine is atypical in that it does not produce ...

Also Ranks for: Dopamine D4 Receptors |  low density |  receptor antagonists |  antipsychotic clozapine |  control brain
KOL Index score: 12314

DOPAMINE receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it1–3. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia4,5. ...

Also Ranks for: Higher Affinity |  dopamine receptor |  competitive blotting |  adenylyl cyclase |  d5 sequence
KOL Index score: 12254

BACKGROUND: The dopamine D2 receptor is the common target for antipsychotics, and the antipsychotic clinical doses correlate with their affinities for this receptor. Antipsychotics quickly enter the brain to occupy 60-80% of brain D2 receptors in patients (the agonist aripiprazole occupies up to 90%), with most clinical improvement occurring within a few days. The D2 receptor can exist in a state of high-affinity (D2(High) ) or in a state of low-affinity for dopamine (D2Low).

AIM: The ...

Also Ranks for: Dopamine Supersensitivity |  d2high receptors |  animal models |  antipsychotics antipsychotic |  clinical improvement
KOL Index score: 12071

A procedure was developed to identify receptors for dopamine and serotonin separately and selectively by means of [3H]spiperone and to measure the density of each receptor in different regions of the rat brain. In the striatum, the binding of [3H]spiperone to dopamine receptors was inhibited by sulpiride but not by quinazolinedone R43448 (R43448); in the frontal cortex, however, the binding of [3H]spiperone to serotonin receptors was inhibited by R43448 but not by sulpiride. Thus, the ...

Also Ranks for: Brain Regions |  serotonin receptors |  kd values |  frontal cortex |  sites striatum
KOL Index score: 11857

OBJECTIVE: Although atypical antipsychotics are becoming the treatment of choice for schizophrenia, what makes an antipsychotic "atypical" is not clear. This article provides a new hypothesis about the mechanism of action of atypical antipsychotics.

METHOD: Published data regarding the molecular, animal model, neuroimaging, and clinical aspects of typical and atypical antipsychotics were reviewed to develop this hypothesis. Particular attention was paid to data regarding the role of the ...

Also Ranks for: Atypical Antipsychotics |  fast dissociation |  new hypothesis |  receptors dopamine |  receptor antagonists
KOL Index score: 11672

Since previous work had shown that brain D2 3,4-dihydroxyphenylethylamine (dopamine) receptors were only partly converted from their high-affinity state to their low-affinity state, we here tested whether it was possible to obtain a complete 100% conversion of these receptors into their low-affinity state. It was first essential to resolve the components of [3H]spiperone binding to dopaminergic sites and nondopaminergic sites in rat striatal homogenates. In the presence of 50 microM ...

Also Ranks for: Affinity State |  dopamine receptors |  sodium ions |  guanine nucleotide |  3hspiperone binding
KOL Index score: 11595

Dopamine receptor types D1 and D2 can oppose or enhance each other's actions for electrical, biochemical, and psychomotor effects. We report a D1-D2 interaction in homogenized tissue as revealed by ligand binding. D2 agonists lowered the binding of [3H]raclopride to D2 receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D1-selective antagonist SCH 23390 prevented the agonist-induced decrease in [3H]raclopride binding to D2 sites in the striatum but not ...

Also Ranks for: Dopamine Receptors |  huntington disease |  affinity state |  anterior pituitary |  d1 link
KOL Index score: 11540

Schizophrenia is a major psychiatric disorder which is hypothesized to result from abnormal neurodevelopment or neural changes in adulthood and possibly associated with altered gene expression. To search for genes overexpressed in schizophrenia, cDNA library subtractive hybridization experiments between post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were carried out. One of the genes over-expressed in schizophrenia was identified as ...

Also Ranks for: Schizophrenia Nogo |  expression regulation |  abnormal neurodevelopment |  3untranslated region |  neurological controls

Key People For Dopamine Receptors

Top KOLs in the world
Philip ******
dopamine receptors antipsychotic drugs rat brain
David * ******
dopamine receptors adenylate cyclase receptor phosphorylation
Jean‐Charles ********
histamine receptors d3 receptor rat brain
Marc * *****
adrenergic receptors adenylate cyclase dopamine transporter
Pierre ********
d3 receptor nucleus accumbens drug addiction
Marie‐Pascale *******
dopamine receptors d3 receptor rat brain

Philip Seeman:Expert Impact

Concepts for whichPhilip Seemanhas direct influence:Dopamine receptors,  Receptors dopamine,  Dopamine receptor,  Dopamine d1,  D2high receptors,  Dopamine d2high,  Antipsychotic drugs,  Dopamine d1 receptors.

Philip Seeman:KOL impact

Concepts related to the work of other authors for whichfor which Philip Seeman has influence:Dopamine receptors,  Nucleus accumbens,  Antipsychotic drugs,  Prefrontal cortex,  Rat brain,  Basal ganglia,  D3 receptor.



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Departments of Pharmacology and Psychiatry, University of Toronto, 260 Heath St. West, unit 605, Toronto, Ontario, M5P 3L6, Canada | University of Toronto | Departments of Pharmacology and Psychiatry, University of Toronto, 260 Heath St. West, unit 6