Biomaterial Database

Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatum. 1992

H Tsuchihashi, and T Sasaki, and S Kojima, and T Nagatomo

Department of Pharmacology, Niigata College of Pharmacy, Japan.

The present study was designed to examine the properties of [3H]haloperidol binding to dopamine D2-receptors in rat striatum membranes, displacement potencies of various chemicals and differences between the affinities of various chemicals and two new 5-hydroxytryptamine (5-HT2) receptor antagonists, MCI-9042, (+/-)-2-(dimethylamino)-1-[[o-(m-methoxyphenetyl)phenoxy]methyl]et hyl hydrogen succinate hydrochloride and one of its metabolites. The plots of specific binding for the striatum membranes obtained from the Scatchard analysis using [3H]haloperidol were monophasic when non-specific binding was determined with 10 microM chlorpromazine, and the Kd and Bmax values were 7.42 +/- 1.03 nM and 1.58 +/- 0.20 pmol (mg protein)-1 (n = 10), respectively. The displacement potencies of D2 receptor, 5-HT2 receptor, histamine H1-receptor, and adrenoceptor antagonists were characterized by [3H]haloperidol binding to D2 receptors. The pKi values of a new antiplatelet agent, MCI-9042, and its metabolite were 5.02 and 5.53, respectively, and these values were lower than those of the D2-receptor antagonists, fluphenazine, spiperone, haloperidol, prochlorperazine, chlorpromazine, thioridazine, and sulpiride. They were also lower than the pKi values of the 5-HT2-receptor antagonists, pirenperone, ketanserin, methysergide, and mianserin. We conclude that the binding site of [3H]haloperidol in the rat striatum is the D2 receptor, that MCI-9042 and its metabolite have lower affinities for D2 receptors than for 5-HT2 receptors, and that this radioreceptor assay is useful for assessing the affinities of various agents.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008566	Membranes	Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.	Membrane Tissue,Membrane,Membrane Tissues,Tissue, Membrane,Tissues, Membrane
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D003342	Corpus Striatum	Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.	Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D005343	Fibrinolytic Agents	Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.	Antithrombic Drug,Antithrombotic Agent,Antithrombotic Agents,Fibrinolytic Agent,Fibrinolytic Drug,Thrombolytic Agent,Thrombolytic Agents,Thrombolytic Drug,Antithrombic Drugs,Fibrinolytic Drugs,Thrombolytic Drugs,Agent, Antithrombotic,Agent, Fibrinolytic,Agent, Thrombolytic,Agents, Antithrombotic,Drug, Antithrombic,Drug, Fibrinolytic,Drug, Thrombolytic,Drugs, Antithrombic
D006220	Haloperidol	A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)	Haldol
D006634	Histamine H1 Antagonists	Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.	Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013386	Succinates	Derivatives of SUCCINIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,4-carboxy terminated aliphatic structure.	Succinic Acids,Acids, Succinic