Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

Journal Article · Fri Feb 01 04:00:00 EST 1985 · Mol. Pharmacol.; (United States)

OSTI ID:5609810

Niznik, H B; Guan, J H; Neumeyer, J L; Seeman, P

In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind (/sup 3/H)spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol.

• Research Organization: Univ. of Toronto, Ontario, Canada
• OSTI ID: 5609810
• Journal Information: Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 27:2; ISSN MOPMA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALI METAL COMPOUNDS
AMIDES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL BONDS
CHLORIDES
CHLORINE COMPOUNDS
COVALENCE
DOPAMINE
DRUGS
ELECTROMAGNETIC RADIATION
HALIDES
HALOGEN COMPOUNDS
HYDROXY COMPOUNDS
INACTIVATION
LABELLING
LIGANDS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
PHOTOSENSITIVITY
POLYPHENOLS
RADIATIONS
RECEPTORS
RESPONSE MODIFYING FACTORS
SENSITIVITY
SODIUM CHLORIDES
SODIUM COMPOUNDS
SYMPATHOMIMETICS
ULTRAVIOLET RADIATION