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Titolo:
Dopamine D-2 receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects
Autore:
Wadenberg, MLG; Soliman, A; VanderSpek, SC; Kapur, S;
Indirizzi:
CAMH, Clarke Div, PET Ctr, Schizophrenia Program, Toronto, ON M5T 1R8, Canada CAMH Toronto ON Canada M5T 1R8 renia Program, Toronto, ON M5T 1R8, Canada CAMH, Sect Biopsychol, Toronto, ON M5T 1R8, Canada CAMH Toronto ON CanadaM5T 1R8 ct Biopsychol, Toronto, ON M5T 1R8, Canada Univ Toronto, Dept Psychiat, Toronto, ON, Canada Univ Toronto Toronto ON Canada ronto, Dept Psychiat, Toronto, ON, Canada
Titolo Testata:
NEUROPSYCHOPHARMACOLOGY
fascicolo: 5, volume: 25, anno: 2001,
pagine: 633 - 641
SICI:
0893-133X(200111)25:5<633:DDROIA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONDITIONED AVOIDANCE-RESPONSE; DOUBLE-BLIND PET; SCHIZOPHRENIC-PATIENTS; ANTAGONIST; RATS; CATALEPSY; SUPPRESSION; L-745,870; CLOZAPINE; 5-HT2;
Keywords:
dopamine; D-2 receptor; antipsychotics; catalepsy; conditioned avoidance response; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Kapur, S CAMH, Clarke Div, PET Ctr, Schizophrenia Program, 250 Coll St, Toronto, ONM5T 1R8, Canada CAMH 250 Coll St Toronto ON Canada M5T 1R8 nto, ONM5T 1R8, Canada
Citazione:
M.L.G. Wadenberg et al., "Dopamine D-2 receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects", NEUROPSYCH, 25(5), 2001, pp. 633-641

Abstract

Conditioned avoidance response (CAR) behavior and catalepsy (CAT) are the standard preclinical tests used to predict antipsychotic activity and motorside-effect liability, respectively. Recent data in patients show that striatal dopamine D-2 occupancy predicts antipsychotic response (at 65% D-2 occupancy) and motor side-effects (at greater than 80%). To relate preclinical and clinical findings, this study examined the relationship between striatal D-2 occupancy, CAT and CAR in rats receiving typical and atypical antipsychotics. CAT was observed in animals receiving haloperidol, risperidone and olanzapine, but only at doses that produced a D, receptor occupancy greater than or equal to 85%. The D-2 occupancy of quetiapine did not cross the85% threshold (up to 100 mg/kg) and it did not show catalepsy. All drugs were effective in the CAR model at a lower level of D-2 occupancy than was required for catalepsy. We suggest that the CAR and CAT models may have displayed high predictive accuracy because they share with the clinical condition a common underlying mechanism: dopamine D-2 occupancy. The implications of this finding for understanding antipsychotic action as well as the continued use of these models in drug discovery is discussed. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.

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Documento generato il 08/12/19 alle ore 12:02:04