Influence of N-alkylation on organ distribution of radioiodinated amphetamines

Conference · Wed May 01 00:00:00 EDT 1985 · J. Nucl. Med.; (United States)

OSTI ID:6758155

Machulla, H J; Schmidt, U; Mehdorn, H M; Knust, E J; Chen, T; Vyska, K

In spite of numerous animal data and the widespread clinical application of p-(I-123)-N-isopropyl-amphetamine, questions remain open about the role of N-alkylation. Therefore, amphetamine (AP), N-methyl- (MeAP), and N-isopropyl-amphetamine (IsAP) were radioiodinated in the para position and the organ distribution was determined in male mice (Freiburg tribe) 10 weeks of age. In the lungs, all derivatives showed principally the same kinetics. In brain, the maximum uptake was reached after 30 min with 12%/g for AP and MeAP, and 10.5%/g for IsAP. In liver, the radioactivity similarly increased during the first 15 min to approx. 12%/g; afterwards, AP clearly decreased but MeAP remained almost constant up to 120 min and, even more, IsAP increased to a maximum of 18%/g at 30 min. The same brain uptake kinetics for all 3 substances exclude the importance of lipophilicity increased by the N-alkylation. Furthermore, the differences in the liver kinetics of AP and both MeAP and IsAP indicate the importance of liver metabolism on the alkylated amphetamines. The results support the hypothesis that the first important metabolite of the N-alkylated derivatives is the amphetamine which accumulates in the brain as do MeAP and IsAP. On the basis of these findings, AP was applied clinically showing the same efficient brain uptake and distribution in SPECT as IsAP.

• Research Organization: Univ. of Essen Medical Center, Essen, St. Josef Hospital, Oberhausen, Heart Center of NRW, Bad Oeynhausen
• OSTI ID: 6758155
• 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

Related Subjects

550602* -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ALKYLATION
AMPHETAMINES
ANALEPTICS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL REACTION KINETICS
CHEMICAL REACTIONS
CHEMISTRY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
DIGESTIVE SYSTEM
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
GLANDS
HALOGENATION
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINATION
IODINE 123
IODINE ISOTOPES
ISOTOPES
KINETICS
LIVER
LUNGS
MAMMALS
MEDICINE
METABOLISM
MICE
NERVOUS SYSTEM
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOACTIVITY
RADIOCHEMISTRY
RADIOISOTOPES
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
STRUCTURE-ACTIVITY RELATIONSHIPS
SYMPATHOMIMETICS
TIME DEPENDENCE
TISSUE DISTRIBUTION
TOMOGRAPHY
UPTAKE
USES
VERTEBRATES