Assessment of dopamine receptor blockade by neuroleptic drugs in the living human brain
Positron emission tomography (PET) makes it possible to attempt to relate directly the antipsychotic effect of neuroleptic drugs and their blocking effect on dopamine receptors (D2) in vivo. The authors have examined the ability of haloperidol (HAL) and molindone (MOL) to block the binding of C-11 n-methylspiperone (NMSP) in 6 normal subjects. A dose of 0.05 mg/kg of HAL resulted in a 68% drop in the slope of the caudate/cerebellum (Ca/Cb) vs. time. This slope is related to the rate of specific binding of NMSP to the receptor. A dose response was seen with both drugs. With increasing doses of HAL from .05 to 0.082 mg/kg, CA/Cb vs. time slope fell from .235 to .156/min. (N=4), progressively. Similarly with increasing doses of MOL of .16-.44 mg/kg slopes decreased from .0335 to .0155/min. (N=4). Similar degrees of post injection Ca/Cb ratio were produced with quantities of MOL and HAL administered in the oral dose ratio of doses 3-5:1 times greater than HAL. This is also the dose ratio at which we found similar dopamine receptor blockade by PET in vivo. A question that arises is why the in vitro affinity of HAL for D2 is 30 times greater than that of MOL in the human brain. The results raise the possibility that MOL metabolites are not only active in blocking D2 but indeed may possibly be more potent than MOL itself. It also helps confirm the site of action of MOL and its in vivo metabolites.
- Research Organization:
- The Johns Hopkins Medical Institutions, Baltimore, MD
- OSTI ID:
- 6795133
- Report Number(s):
- CONF-850611-
- Journal Information:
- J. Nucl. Med.; (United States), Journal Name: J. Nucl. Med.; (United States) Vol. 26:5; ISSN JNMEA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
BODY AREAS
BRAIN
CARBON 11
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHEMISTRY
COMPUTERIZED TOMOGRAPHY
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVALUATION
EVEN-ODD NUCLEI
HEAD
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
LIGHT NUCLEI
MAMMALS
MAN
MEMBRANE PROTEINS
METABOLISM
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PERFORMANCE
PHENOLS
POLYPHENOLS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
PSYCHOTROPIC DRUGS
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIONUCLIDE KINETICS
RADIORECEPTOR ASSAY
RECEPTORS
SCINTISCANNING
SYMPATHOLYTICS
SYMPATHOMIMETICS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
VERTEBRATES