Biomaterial Database

Rat brain binding sites for pramipexole, a clinically useful D3-preferring dopamine agonist. 1995

M Camacho-Ochoa, and E L Walker, and D L Evans, and M F Piercey

CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001, USA.

Pramipexole (PPX) is currently being evaluated for treatment of schizophrenia and Parkinson's disease. In studies with cloned subtypes of the dopamine (DA) D2 receptor subfamily, PPX has higher affinity for the D3 compared to the D2 and D4 subtypes; unlike 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), it does not bind to sigma sites. Receptor binding autoradiography with [3H]PPX (5 nM, 62 Ci/mmol) was used to evaluate the distribution of PPX binding sites within the rat brain. Consistent with its preference for D3-binding sites, the highest concentrations of [3H]PPX binding sites were found in the islets of Calleja (ICj), previously reported to contain D3 but not D2 or D4 mRNA. [3H]PPX binding was also high in other mesolimbic areas such as the nucleus accumbens (N. accum), olfactory tubercle, and amygdala. [3H]PPX binding was also high in caudate (Cd), although slightly less than in mesolimbic areas. Less [3H]PPX binding sites were found in ventral tegmental area (VTA) and substantia nigra, areas rich in cell bodies for DA neurons. Thus, although PPX most potently stimulates DA autoreceptors, PPX binding sites have their highest concentrations in projection areas containing both DA terminal and postsynaptic receptors. Because of PPX's preferential affinity for the D3 receptor subtype and its resultant high mesolimbic binding, it could have a unique therapeutic profile for treatment of psychiatric and/or neurological diseases.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010300	Parkinson Disease	A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D000077487	Pramipexole	A benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of PARKINSON DISEASE and RESTLESS LEGS SYNDROME.	2-Amino-4,5,6,7-tetrahydro-6-propylaminobenzothiazole,2-Amino-6-propylaminotetrahydrobenzothiazole,4,5,6,7-Tetrahydro-N6-propyl-2,6-benzothiazole-diamine,6,7-Tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydrochloride monohydrate,Mirapex,Pramipexol,Pramipexol Dihydrobromide, (+-)-isomer,Pramipexol Dihydrochloride, (S)-isomer,Pramipexol, (+-)-isomer,Pramipexole Dihydrochloride,Pramipexole Dihydrochloride Anhydrous,Pramipexole Hydrochloride Monohydrate,SND-919,Sifrol,2 Amino 6 propylaminotetrahydrobenzothiazole,SND 919
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
D001345	Autoradiography	The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)	Radioautography
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012559	Schizophrenia	A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.	Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D013764	Tetrahydronaphthalenes	Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.	Tetralins