Drug combo induces hypothermia in mice, hints at stroke treatment

A pair of older drugs pushed mice into hypothermia and cut brain injury after stroke, a striking result that highlights both the promise and the limits of drug-based cooling. The combination, chlorpromazine plus promethazine, lowered metabolism, dilated blood vessels and reduced the size of infarcts in a mouse stroke model.

The work matters because cooling has long been seen as a way to protect brain tissue after blood flow is blocked. Lower temperatures slow the cascade of damage that follows a stroke, but delivering that protection in a hospital has been difficult. External cooling can be slow, hard to control and can trigger shivering, which is one reason the field has looked for a pharmacological route instead.

In the new study, published online June 17, 2026, in Science Translational Medicine, the drug pair, abbreviated C+P, reduced glucose metabolism in the mouse brain, improved neurological deficits after middle cerebral artery occlusion and showed cerebroprotective effects in a rhesus monkey stroke model. The authors include Shuaili Xu, Qi Wang, Hong An, Hao Wang, Qiang Fang, Tao Li, Qinqin He, Jian Zhou, Jian Chen, Yu Liang, Miaowen Jiang, Ming Li, Huan Zhang, Yuchuan Ding, Shiao Li, Fengyuan Che, Chuanjie Wu, Xunming Ji and Di Wu, with the work centered on Capital Medical University and Xuanwu Hospital in Beijing.

The study’s strongest sign of translation came from a double-blind phase 1 trial, NCT06663631, which enrolled 32 patients with acute ischemic stroke and tested placebo or escalating doses of C+P at 10, 20, 50 or 100 milligrams. That step does not make the drugs a treatment yet, but it does move the idea beyond a mouse-only claim and into human safety testing.

The public-health stakes are large. The Centers for Disease Control and Prevention says about 87% of all strokes are ischemic, more than 795,000 people in the United States have a stroke each year, and stroke costs the country nearly $56.2 billion annually. Stroke is also a leading cause of serious long-term disability. Globally, the World Stroke Organization says stroke remains the second leading cause of death and the third leading cause of death and disability combined.

Still, the road to bedside use is long. A 2016 Stroke study found that combining physical cooling with the neurotensin receptor 1 agonist HPI-201 improved hypothermia and reduced infarct formation in rats, while also noting the practical problems of external cooling in humans. A 2024 systematic review found 25 animal studies of therapeutic hypothermia with pharmacological cotreatments, but also high risk of bias and a need for confirmatory work. The American Heart Association says some clot-busting and clot-removal windows now extend up to 24 hours after symptom onset when imaging shows salvageable tissue, a reminder that stroke care is already racing the clock.

For now, C+P looks less like a ready-made therapy than a carefully advanced test of whether cooling can be made faster, safer and more selective. That is the real hurdle between an eye-catching animal result and something that can help patients in emergency rooms.