The Impact of Efflux Transporters in the Brain on the Development of Drugs for CNS Disorders
| Autor: | Eve M. Taylor |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Drug
ATP Binding Cassette Transporter Subfamily B media_common.quotation_subject Central nervous system Biological Transport Active ATP-binding cassette transporter Pharmacology Blood–brain barrier Central Nervous System Diseases medicine Monocarboxylic Acid Transporters Humans Pharmacology (medical) P-glycoprotein media_common biology Membrane Transport Proteins Transporter Drug Resistance Multiple medicine.anatomical_structure Blood-Brain Barrier Drug Design biology.protein Efflux Multidrug Resistance-Associated Proteins |
| Zdroj: | Clinical Pharmacokinetics. 41:81-92 |
| ISSN: | 0312-5963 |
| DOI: | 10.2165/00003088-200241020-00001 |
| Popis: | The development of drugs to treat disorders of the CNS requires consideration of achievable brain concentrations. Factors that influence the brain concentrations of drugs include the rate of transport into the brain across the blood-brain barrier (BBB), metabolic stability of the drug, and active transport out of the brain by efflux mechanisms. To date, three classes of transporter have been implicated in the efflux of drugs from the brain: multidrug resistance transporters, monocarboxylic acid transporters, and organic ion transporters. Each of the three classes comprises multiple transporters, each of which has multiple substrates, and the combined substrate profile of these transporters includes a large number of commonly used drugs. This system of transporters may therefore provide a mechanism through which the penetration of CNS-targeted drugs into the brain is effectively minimised. The action of these efflux transporters at the BBB may be reflected in the clinic as the minimal effectiveness of drugs targeted at CNS disorders, including HIV dementia, epilepsy, CNS-based pain, meningitis and brain cancers. Therefore, modulation of these efflux transporters by design of inhibitors and/or design of compounds that have minimal affinity for these transporters may well enhance the treatment of intractable CNS disorders. |
| Databáze: | OpenAIRE |
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