Antidepressant May Enhance Drug Delivery to the Brain Interview with:

Ronald Cannon, Ph.D. Staff scientist at NIH’s National Institute of Environmental Health Sciences

Dr. Cannon

Ronald Cannon, Ph.D.
Staff scientist at NIH’s National Institute of Environmental Health Sciences What is the background for this study?

Response: The protein pump, P-glycoprotein, is a major obstacle to the delivery of therapeutic drugs across the blood-brain barrier and into the central nervous system (CNS). During the last 10 years, our laboratory has studied the regulation of P-glycoprotein with the hope of treating CNS diseases. What are the main findings?

Response: Our most recent finding shows that the antidepressant, amitriptyline, suppresses P-glycoprotein pump activity. The discovery is significant because P-glycoprotein restricts most CNS targeted drugs from entering the brain. If fully translatable to human patients, suppression of P-glycoprotein could allow higher levels of CNS therapeutic drugs to reach their intended target. What should readers take away from your report?

Response: Understanding the molecular mechanisms that regulate the blood-brain barrier will hopefully allow for better drug design and improved delivery systems to treat CNS diseases. What recommendations do you have for future research as a result of this study?

Response: To fully implement our findings into the clinic, future studies should focus on two main objectives:
1) Determine the types of CNS drugs most appropriate to be co-administered with amitriptyline.
2) Determine the appropriate doses of both amitriptyline and the co-administered drug that will produce the bests therapeutic outcome for the patient. Is there anything else you would like to add?

Response: This study is an extension of work pioneered by scientist David S. Miller, Ph.D., former head of the Signal Transduction Laboratory, and Intracellular Regulation Group at the National Institute of Environmental Health Sciences (NIEHS). Prior to retirement, Dr. Miller was head of the lab that contributed to the assays and strategies that allowed these discoveries. We and others owe him a debt of gratitude. This work would have not been possible without his earlier accomplishments.

Provisional Patent Application Number:
62453718 – “Methods for Improving Drug Delivery Across the Blood-Brain Barrier” Thank you for your contribution to the community.


Banks DB, Chan GNY, Evans RA, Miller DS, Cannon RE. 2017. Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce p-glycoprotein transport at the blood-brain-barrier. J Cereb Blood Flow Metab; doi:10.1177/0271678X17705786 [Online 27 April 2017].

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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