- Person
- Julius Axelrod
- Lived
- 1912–2004
- Field
- Pharmacology, neuroscience
- From
- American
The story
Nerve cells pass signals by releasing chemical messengers, or neurotransmitters, across the gap to the next cell. In the 1950s scientists assumed that once a messenger had done its work, enzymes destroyed it. Julius Axelrod, head of a one-man pharmacology section at the US National Institute of Mental Health, himself discovered one such enzyme, catechol-O-methyltransferase, in 1957. Yet blocking the known enzymes did not stop the effects of adrenaline and noradrenaline, so something else had to be switching the signal off.
Given radioactively labelled adrenaline and noradrenaline, Axelrod injected them into animals and traced where they went. With colleagues he found that the messengers concentrated in organs rich in sympathetic nerves, such as the heart and spleen, and that when those nerves were cut on one side of the body, the uptake on that side disappeared. He concluded that noradrenaline is taken back up into the nerve endings that released it, stored and used again. Reuptake is now regarded as the most common way chemical signalling between nerves is ended.
Axelrod then tested drugs. Cocaine, amphetamine and the tricyclic antidepressants all blocked reuptake, which explained how they strengthen the effects of nerve signals. With his postdoctoral fellows Jacques Glowinski and Leslie Iversen he showed that antidepressants’ ability to block noradrenaline uptake in the brain matched their effectiveness as medicines. Axelrod shared the 1970 Nobel Prize in Physiology or Medicine with Bernard Katz and Ulf von Euler; his share recognised the discovery of reuptake.
The principle shaped psychiatry for decades. Drug developers went on to design medicines that block the reuptake of serotonin selectively, the SSRIs such as fluoxetine (Prozac), and later drugs that block serotonin and noradrenaline reuptake together. His biographer Solomon Snyder wrote that inhibition of amine uptake remains the accepted mechanism of the tricyclic antidepressants and drove the development of several generations of new antidepressants.
Why it matters
Antidepressants that work by blocking reuptake, including the SSRIs, are used by many millions of people with depression and anxiety, building on Axelrod’s discovery.
About Julius Axelrod
Son of Jewish immigrants who helped identify acetaminophen as a safe painkiller and found how nerves recycle their chemical messengers, the basis of modern antidepressants. Nobel Prize 1970.
More about Julius Axelrod
Sources
- Julius Axelrod, Biographical Memoir by Solomon H. Snyder National Academy of Sciences
- Julius Axelrod Wikipedia
- Julius Axelrod dies The Scientist
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