Delivering drugs via the brain

Gavril Pasternak of the Memorial Sloan-Kettering Cancer Center, New York, and co-workers examined the pharmacological progress of drugs, such as opioids, when injected into the brain. They report in 1 March Nature Neuroscience, that the drugs are pumped out of the brain into the systemic circulation by the multi-drug resistance transporter Mdr1a (also known as P-glycoprotein 1), a protein that is also implicated in the resistance of tumour cells to chemotherapy.

When mdr1a expression was lost, as in mdr1a knockout mice, or downregulated by means of antisense treatment, the export of drugs from the brain to the systemic circulation was reduced (Nat Neurosci 2001, 4:268-274). Conversely, drugs delivered systemically had increased access to the brain when mdr1a expression was absent or reduced, suggesting Mdr1a normally helps to maintain the blood–brain barrier.

In an accompanying News & Views article, Robert Edwards of the UCSF School of Medicine, San Francisco, discusses the ...