Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine.
The present study was conducted to characterize the binding of neurotransmitter receptors (dopamine D(2), serotonin 5-HT(2), histamine H(1), adrenaline alpha(1) and muscarine M(l) receptors) in the rat's brain after the oral administration of haloperidol, risperidone, and olanzapine. Haloperidol at 1 and 3 mg/kg displayed significant activity to bind the D(2) receptor (increase in the Kd value for [(3)H]raclopride binding) in the corpus striatum with little change in the activity toward the 5-HT(2) receptor (binding parameters for [(3)H]ketanserin). In contrast, risperidone (0.1-3 mg/kg) showed roughly 30 times more affinity for the 5-HT(2) receptor than D(2) receptor. Also, olanzapine (1-10 mg/kg) was most active toward the H(1) receptor in the cerebral cortex, corpus striatum, and hippocampus, was less active in binding 5-HT(2) and D(2) receptors, and showed the least affinity for alpha(1) and M(1) receptors. In conclusion, haloperidol and risperidone administered orally selectively bind D(2) and 5-HT(2) receptors, respectively, in the rat brain, while olanzapine binds H(1), 5-HT(2), and D(2) receptors more than alpha(1) and M(1) receptors.
Uchida
Shinya
S
Department of Pharmacokinetics and Pharmacodynamics and Center of Excellence (COE) Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Kato
Yasuhiro
Y
Hirano
Kazufumi
K
Kagawa
Yoshiyuki
Y
Yamada
Shizuo
S
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D000077152:Olanzapine; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D017983:Receptors, Catecholamine / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D018967:Risperidone / Q000008:administration & dosage*
D014150:Antipsychotic Agents; D043643:Receptor, Muscarinic M1; D017983:Receptors, Catecholamine; D017981:Receptors, Neurotransmitter; D044348:Receptors, Serotonin, 5-HT2; D001569:Benzodiazepines; D007650:Ketanserin; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine