Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Patent
1997-04-01
1999-06-29
Dees, Jose' G.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
424 145, 424 111, A61K 5100, A61M 3614
Patent
active
059165375
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a diagnostic comprising a labeled transmitter substance of a central nervous system or a labeled precursor of the transmitter substance, whose a specific carbon atom is replaced by a carbon isotope, which is used for diagnosing a central nervous abnormality and phenylketonuria by measuring an amount of the carbon isotope in a breath of the living body to which the diagnosis has been administered, and a diagnosis method using the above diagnostic.
BACKGROUND ART
Heretofore, various morbidities with respect to a central nerve, such as depression, Alzheimer's disease, schizophrenia, etc. have been generally referred to as a "central nervous abnormality". Various pharmacological and biological studies on this central nervous abnormality have been made, and the study on a novel drug for treating these diseases by normalizing a metabolic change has also been made.
Phenylketonuria is a morbidity caused by dysbolism of phenylalanine.
However, the elucidation of the mechanism of pathopoiesis and metabolic change have never been sufficiently conducted, and a method for simply and precisely diagnosing these diseases has never been established.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to provide a method for simply and precisely diagnosing diseases which are generally referred to as a central nervous abnormality and phenylketonuria, and a diagnosis used for diagnosing these diseases.
The present inventors have intensively studied so as to accomplish the above object. As a result, it has been found that, when a drug containing, as an active ingredient, a labeled transmitter substance of a central nervous system or a labeled precursor of the transmitter substance, whose at least one carbon atom is substituted for a carbon isotope, is administered to a living body and then an amount of carbon isotope in a breath is measured, the amount of carbon isotope reflects the central nervous abnormality and, therefore, the above drug is useful as a diagnostic for central nervous abnormality. Accordingly, when using this diagnostic, the central nervous abnormality can be simply, quickly and very precisely diagnosed by a simple operation without accompanying invasion of a subject.
That is, according to the present invention, there is provided a diagnostic for diagnosing central nervous abnormality, comprising the labeled transmitter substance of the central nervous system or a labeled precursor of the transmitter substance, whose at least one carbon atom is substituted for the carbon isotope, wherein the diagnostic is used for diagnosing central nervous abnormality by applying the diagnostic to a living body due to oral administration or injection, and examining a change in the amount of the carbon isotope in a breath of the living body. Further, there is also provided a diagnosis method using the diagnostic mentioned above.
Phenylalanine, which is included in the transmitter substance of central nervous system or its precursor, is related to phenylketonuria. Therefore, when a drug containing phenylalanine labeled with a carbon isotope at at least one of the 1-position, 2-position and 3-position of the side chain as an active ingredient is administered to a living body and then an amount of carbon isotope in a breath of the living body is measured, the amount of carbon isotope reflects the phenylketonuria. Therefore, the above drug is also useful as a diagnostic for phenylketonuria. Accordingly, when using this diagnostic, the phenylketonuria can be easily, quickly and very precisely diagnosed by a simple operation without accompanying invasion of a subject.
That is, according to the present invention, there are provided a diagnostic for phenylketonuria, comprising phenylalanine labeled with a carbon isotope at at least one of the 1-position, 2-position and 3-position of the side chain as an active ingredient, wherein the diagnostic is used for diagnosing a phenylketonuria by applying the diagnostic to the living body by oral administration or inject
REFERENCES:
patent: 5320825 (1994-06-01), Kung
patent: 5386832 (1995-02-01), Wagner et al.
patent: 5707602 (1998-01-01), Klein
P. Klein, et al., "The Commercial Feasibility of C .sup.13 Breath Tests," Analytical Chemistry Symposium Series, vol. 11, (1982), pp. 347-353.
N. Matsuoka, et al., "Effect of FR 121196, a Novel Cognitive Enhancer, on the Memory Impairment of Rats in Passive Avoidance and Radial Arm Maze Tasks," J. Pharmacol, Exp. Ther., vol. 263, No. 2(1992), pp. 436-445.
G.H. Dodd, "The Lipid Membrane Hypothesis of Schizophrenia: Implications for Possible Clinical Breath Tests," Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 55, Nos. 1 and 2 (1996), pp. 95-99.
H.G. Broesicke, et al., Chemical Abstracts, Abstract No. 23791, vol. 119, Jul. 19, 1993. to Respiratory .sup.14 CO.sub.2 in Healthy Subjects, Phenylketonuria Heterozygotes and Classic Phenylketonurics," Clinica Chimica Acta., vol. 157, No. 3 (1986), pp. 253-266.
N. Tran-Manh, et al., "Abnormalities in .sup.14 CO.sub.2 Production from DL-3,4-Dihydroxyphenylalanine-arboxyl-.sup.14 C in Schizophrenia and Parkinsonism: A Preliminary Report," Rev. Can. Biol., vol. 31, Supp. (1972), pp. 255-262.
C. Godin, et al., "Tryptophan Metabolism in Normal and Phenylketonuric Rats," Biochim. Biophys. Acta, vol. 130 (1966), pp. 535-537.
J.F. Dellaria, Jr., et al., "Stereoselective Alkylation of Chiral Glycine Enolate Synthons. The Enantioselective Synthesis of .alpha.-Amino Acid Derivatives," Tetrahedron Letters, vol. 29, No. 47 (1988), pp. 6079-6082.
J.L. Howard, et al., "Empirical Behavioral Models of Depression, with Emphasis on Tetrabenazine Antagonism," Antidepressants: Neurochemical, Behavioral, and Clinical Perspectives, (Eds. S.J. Enna, Ph.D., et al.) Raven Press, New york, 1981, pp. 107-120.
D.A. Schoeller, et al., "A Microprocessor Controlled Mass Spectrometer for the Fully Automated Purification and Isotopic Analysis of Breath Carbon Dioxide," Biomedical Mass Spectrometry, vol. 6, No. 8 (1979), pp. 350-355.
P.D. Klein, et al., "Applications of Stable Isotopes to Pediatric Nutrition and Gastroenterology: Measurement of Nutrient Absorption and Digestion Using .sup.13 C," Journal of Pediatric Gastroenterology and Nutrition, vol. 4 (1985), pp. 9-19.
C.J.E. Niemegeers, et al., "Interaction of Drugs with Apomorphine, Tryptamine and Norepinephrine. A New "in vivo" Approach: the ATN-Test in Rats," Arch. int. Pharmacodyn, vol. 227 (1977), pp. 238-253.
A.J. Puech, et al., "Pharmacological Properties of New Antipsychotic Agents: use of Animal Models," Neuropharmacol., vol. 20 (1981), pp. 1279-1284.
L. Davis, et al., "Substituted (Pyrroloamino) pyridines: Potential Agents for the Treatment of Alzheimer's Disease," J. Med. Chem., vol. 39, No. 2 (1996), pp. 582-587.
Hirose Tsuyoshi
Ikei Nobuhiro
Kajiwara Masahiro
Dees Jos,e G.
Jones Dameron
Otsuka Pharmaceutical Co. Ltd.
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