Rodent of the week: Gabapentin may be unsafe for developing brains

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A study performed in mice and in cell culture suggests that the heavily prescribed drug gabapentin halts the formation of new synapses, or nerve connections, in the brain. That ability may be the reason the drug is effective in treating epileptic seizures and pain. But the findings also suggest that the medication may harm fetuses and young children, whose brains are still developing.

Stanford University researchers examined the interaction between neurons and brain cells called astrocytes. Previous studies showed that a protein that astrocytes secrete, thrombospondin, is critical to the formation of the brain’s circuitry. In the study, researchers found that thrombospondin binds to a receptor, called alpha2delta-1, on the outer membrane of neurons. In a study in mice, they showed that the neurons that lacked alpha2delta-1 could not form synapses in response to the presence of thrombospondin.

Alpha2delta-1 is the receptor for gabapentin. That has been known, although scientists did not understand how gabapentin worked. But the new research revealed that when gabapentin was given to mice, it prevented thrombospondin from binding to the receptor, thus stopping the synapse formation.

While gabapentin, which is sold under the trade name Neurontin, does not dissolve pre-existing synapses, it prevents the formation of new ones. That’s why the medication may be dangerous if given to pregnant women or young children, the authors said. The majority of the brain’s synapses are formed in utero and early childhood.

‘It’s a bit scary that a drug that can so powerfully block synapse formation is being used in pregnant women,’ Dr. Ben Barres, a professor of neurobiology and the senior author of the study, said in a news release. ‘This potential effect on fetal brains needs to be taken seriously. Right now, doctors have the view that gabapentin is the safest anticonvulsant. There is no question that pregnant women with epilepsy who have been advised by their neurologists to continue their anticonvulsant treatment with gabapentin during their pregnancy should definitely remain on this drug until instructed otherwise. But there is no long-term registry being kept to track gabapentin-exposed babies. Our findings are saying that we need to be following up on these newborns so that their cognitive performance can be studied as they grow older.’

The study is published online in the journal Cell.

-- Shari Roan