Dopamine D2 receptor agonists protect against ischaemia-induced hippocampal neurodegeneration in global cerebral ischaemia. 1998

M J O'Neill, and C A Hicks, and M A Ward, and G P Cardwell, and J M Reymann, and H Allain, and D Bentué-Ferrer
Eli Lilly, Lilly Research Centre, Windlesham, Surrey, UK. oneill_michael-j@lilly.com

To characterise the role played by dopamine receptors in ischaemic brain damage, we have evaluated the effects of pergolide, bromocriptine and lisuride (dopamine D2 receptor agonists), haloperidol (a dopamine D2 receptor antagonist), 2,3,4,5-tetrahydro-7,8,dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393; a dopamine D1 receptor agonist) and (R)-(+)-8-chloro 2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SCH 23390; a dopamine D1 receptor antagonist) in the gerbil model of global cerebral ischaemia. Ischaemia was induced by 5 min of bilateral carotid artery occlusion under halothane anaesthesia. Sham operated animals were used as controls. Pergolide (0.5 or 1.0 mg/kg i.p), bromocriptine (0.5 or 1.0 mg/kg i.p.), lisuride (0.5 or 1.0 mg/kg i.p.), SCH 23390 (0.1 or 1.0 mg/kg i.p.), haloperidol (0.5, 1.0 or 2 mg/kg i.p.) and SKF 38393 (1.0 or 2 mg/kg i.p.) were administered 1 h before occlusion. Five-minute-occluded animals had extensive damage in the CA1 region of the hippocampus 5 days after surgery. Pergolide 0.5 and 1.0 mg/kg i.p. provided significant (P < 0.05 and P < 0.01, respectively) neuroprotection against the ischaemia-induced hippocampal damage. Bromocriptine and lisuride also provided significant (P < 0.05) neuroprotection, but only at the higher 1.0 mg/kg dose. In contrast, the dopamine D2 receptor antagonist (haloperidol), the dopamine D1 receptor agonist (SKF 38393) and the dopamine D1 receptor antagonist (SCH 23390) failed to provide any neuroprotection in the model. These results support studies indicating that dopamine is important in ischaemic situations. The results also indicate that dopamine D2 receptor agonists are neuroprotective against ischaemia-induced brain injury and may play a role in neurodegenerative disorders.

UI MeSH Term Description Entries
D008090 Lisuride An ergot derivative that acts as an agonist at dopamine D2 receptors (DOPAMINE AGONISTS). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (SEROTONIN RECEPTOR AGONISTS). Lysuride Hydrogen Maleate,Methylergol Carbamide,Arolac,Cuvalit,Dopergin,Dopergine,Lisuride Hydrochloride,Lisuride Maleate,Lisuride Maleate (1:1),Lisuride Maleate, (8beta)-Isomer,Lisuride Mesylate,Lisuride Phosphate (1:1),Lisuride, (8alpha)-(+-)-Isomer,Lysenyl,Lysurid,Revanil,Carbamide, Methylergol,Hydrochloride, Lisuride,Hydrogen Maleate, Lysuride,Maleate, Lisuride,Mesylate, Lisuride
D010479 Pergolide A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES. Celance,LY-127,809,LY-127809,Parkotil,Pergolide Mesylate,Permax,Pharken,LY127,809,LY127809,Mesylate, Pergolide
D001971 Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. 2-Bromoergocryptine,Bromocryptin,2-Bromo-alpha-ergocryptine,2-Bromo-alpha-ergokryptine,2-Bromoergocryptine Mesylate,2-Bromoergocryptine Methanesulfonate,2-Bromoergokryptine,Bromocriptin,Bromocriptine Mesylate,CB-154,Parlodel,2 Bromo alpha ergocryptine,2 Bromo alpha ergokryptine,2 Bromoergocryptine,2 Bromoergocryptine Mesylate,2 Bromoergocryptine Methanesulfonate,2 Bromoergokryptine,CB 154,CB154,Mesylate, 2-Bromoergocryptine,Mesylate, Bromocriptine,Methanesulfonate, 2-Bromoergocryptine
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D005849 Gerbillinae A subfamily of the Muridae consisting of several genera including Gerbillus, Rhombomys, Tatera, Meriones, and Psammomys. Gerbils,Jird,Meriones,Psammomys,Rats, Sand,Gerbil,Jirds,Merione,Rat, Sand,Sand Rat,Sand Rats
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
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
D001552 Benzazepines Compounds with BENZENE fused to AZEPINES.
D015647 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine A selective D1 dopamine receptor agonist used primarily as a research tool. 1H-3-Benzazepine-7,8-diol, 2,3,4,5-tetrahydro-1-phenyl-,R-SK&F 38393,SK&F-38393,SKF 38393-A,SKF-38393,SKF38393,RSK&F 38393,SK&F 38393,SK&F38393,SKF 38393,SKF 38393 A,SKF 38393A

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