Common antipsychotic drug for methamphetamine overdose may damage brain cells

May 30 2007

A common antipsychotic drug used in emergency rooms to treat methamphetamine overdose damages nerve cells in an area of the brain known to regulate movement, a new study shows.

The findings, derived from experiments with rats, indicate that only the combination of the medication, haloperidol, and methamphetamine causes the destructive effects, not either one alone. Senior author Bryan Yamamoto, PhD, and his team at Boston University School of Medicine suspect the damage results from the exaggerated stimulation of cells by the amino acid glutamate, which proves toxic to cells producing the neurotransmitter gamma-aminobutyric acid (GABA). Their results are published in the May 30 issue of The Journal of Neuroscience .

"This work in laboratory animals raises immediate concerns that a standard treatment for methamphetamine overdose in humans might worsen drug abuse-related brain injuries," says William Carlezon, PhD, at Harvard's McLean Hospital, who was not affiliated with the study. "A crucial next step is to determine how atypical antipsychotic medications would affect methamphetamine toxicity in the same model."

The rats in the experiment were injected with either methamphetamine or a saline solution over a period of eight hours. When the rats were given haloperidol before and nearly halfway through the eight-hour period, Yamamoto and his colleagues noted more than a fivefold rise in base levels of glutamate in the substantia nigra, a part of the brain known to play a role in movement disorders such as Huntington's disease.

After examining the long-term effects of the combination, they found that glutamate concentrations in the substantia nigra were twice as high in methamphetamine-treated rats as in saline-treated ones two days after injections. Yamamoto and his colleagues were able to link this rise in glutamate to the death of GABA-containing cells in one part of the substantia nigra. This may predispose some people who have been treated for a methamphetamine overdose to seizures and the development of movement disorders, they say, although the study did not measure movement specifically.

In addition to future studies of other antipsychotic medications, says Yamamoto, "we hope to examine if the loss of cells results in abnormal involuntary movements resembling Tourette's syndrome and Huntington's disease."