Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro.

Article Details

Citation

Richelson E, Nelson A

Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro.

Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204.

PubMed ID
6149136 [ View in PubMed
]
Abstract

Using radioligand binding techniques, we determined the equilibrium dissociation constants (KD's) for a series of neuroleptics at the dopamine (D-2), muscarinic, histamine H1, alpha 1- and alpha 2-adrenergic receptors of normal human brain tissue obtained at autopsy. Seventeen different compounds were studied at the D-2 receptor and 15 compounds at the remaining receptors. At the D-2 receptor of caudate nucleus, spiperone was the most potent compound (KD = 0.16 nM); clozapine the least potent (KD = 180 nM). The KD's for six compounds at the D-2 receptor of nucleus accumbens were not significantly different from their respective KD's in the caudate nucleus. The most potent and least potent compounds at the other receptors were clozapine and molindone at the muscarinic receptor, mesoridazine and molindone at the H1 receptor, spiperone and molindone at the alpha 1-receptor, and clozapine and haloperidol at the alpha 2-receptor, respectively.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ChlorpheniramineHistamine H1 receptorKi (nM)15N/AN/ADetails
ChlorpromazineHistamine H1 receptorKi (nM)9N/AN/ADetails
ClozapineAlpha-2A adrenergic receptorKi (nM)160N/AN/ADetails
ClozapineHistamine H1 receptorKi (nM)2.8N/AN/ADetails
ClozapineMuscarinic acetylcholine receptor M2Ki (nM)12N/AN/ADetails
LoxapineAlpha-2A adrenergic receptorKi (nM)2400N/AN/ADetails
LoxapineHistamine H1 receptorKi (nM)4.9N/AN/ADetails
LoxapineMuscarinic acetylcholine receptor M2Ki (nM)450N/AN/ADetails
PromazineHistamine H1 receptorKi (nM)2N/AN/ADetails
YohimbineAlpha-2A adrenergic receptorKi (nM)2.7N/AN/ADetails
YohimbineAlpha-2A adrenergic receptorKi (nM)1.6N/AN/ADetails