Biomaterial Database

Persistent depletion of striatal dopamine and its metabolites in mice by TMMP, an analogue of MPTP. 1987

R W Fuller, and S K Hemrick-Luecke

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.

TMMP (1-methyl-4-[methylpyrrol-2-yl]-1,2,3,6-tetrahydropyridine) mimicked MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in causing persistent depletion of striatal dopamine and its metabolites one week after the last of four daily subcutaneous injections in mice. MMPP (1-methyl-4-[1-methylpyrrol-2-yl]-4-piperidinol) produced no depletion of dopamine or its metabolites under these conditions. None of the three compounds affected dopamine or its metabolites when administered orally. TMMP was even more rapidly oxidized by type B monoamine oxidase in-vitro than was MPTP, but MMPP was a very poor substrate for the enzyme. The lack of neurotoxicity of MMPP toward nigrostriatal dopamine neurons when it was given orally or subcutaneously to mice contrasts with previously reported results in monkeys, in which case MMPP was reported to be neurotoxic.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006719	Homovanillic Acid	A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.	3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic
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
D015102	3,4-Dihydroxyphenylacetic Acid	A deaminated metabolite of LEVODOPA.	DOPAC,Homoprotocatechuic Acid,3,4-Dihydroxyphenylacetic Acid, Monosodium Salt,3,4 Dihydroxyphenylacetic Acid
D015632	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine	A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.	MPTP,N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine