The identification of two new dopamine receptors may lead tothe development of better drugs to treat Parkinson's diseaseand schizophrenia.

Researchers at the University of Toronto and their colleaguesreport in two papers in today's issue of Nature the cloning ofhuman dopamine receptors D4 and D5.

D4, which is similar to dopamine receptors D2 and D3, binds tothe anti-schizophrenia drug clozapine 10 times as well aseither D2 or D3.

Clozapine, which is also used to treat socially withdrawnpeople, has fewer side effects than other anti-psychoticmedicines. However, clozapine reduces the body's supply ofgranulocyte white blood cells. The researchers propose usingD4 to design drugs that have the efficacy of clozapine, but thatdo not cause white cell depletion.

D5, which is quite similar to dopamine receptor D1, bindsdopamine 10 times better than D1 does. Both D1 and D5 are thelikely targets for anti-Parkinsonism drugs such as L-dopa.Parkinson's disease is a neuromuscular disorder caused by toolittle dopamine in the brain. An understanding of how dopamineinteracts with its receptors may lead to better drugs to treatthe disease.

D1 and D5 receptors differ from D2, D3 and D4 receptors inthat D1 and D5 receptors activate a key metabolic enzyme,adenylate cyclase. D2, D3 and D4 block adenylate cyclaseactivity. The enzyme converts the high-energy compoundadenosine triphosphate (ATP) into the metabolic regulatorcyclic adenosine monophosphate (cAMP).

-- Carol Talkington Verser, Ph.D. Special to BioWorld

(c) 1997 American Health Consultants. All rights reserved.

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