Drug cooling in trials targets stroke brain damage

promethazine and – Two long-used drugs for hay fever and psychosis lowered core body temperature in mice and rhesus monkeys after induced strokes, reducing brain damage. Early human testing with 32 recent stroke patients showed only a small temperature drop of 0.3°C and no reduc

For decades. researchers have chased a terrifyingly narrow window after a stroke: cool the brain fast enough to slow the cascade of injury—before blood flow is restored. The latest approach doesn’t rely on ice or blankets. Instead, it uses two familiar drugs to induce a controlled chill inside the body.

In experiments in mice and rhesus monkeys. researchers combined promethazine and chlorpromazine. medications known since the 1950s to reduce body temperature. After induced strokes. the drug combination cooled the animals’ core temperature. suppressed glucose metabolism in cells. and lessened the amount of brain damage. The reduction wasn’t just measured in tissue—treated monkeys also showed better use of their limbs.

The concept is rooted in a simple. urgent goal: if brain cells can be kept alive until blood flow returns. a patient may be spared extensive brain damage and the speech and movement problems that can follow. Scientists have long described ways to push brain cells into a hibernation-like state so they don’t need as much oxygen and glucose when a stroke cuts off their blood supply. The problem has been getting the cooling deep enough, fast enough, and in a way patients can actually tolerate.

Physical cooling strategies have struggled. Cooling blankets, ice packs, and helmets have failed to work well because they cause intense discomfort and uncontrollable shivering. Kirsten Coupland. at the University of Newcastle in Australia. who wasn’t involved in the study. said shivering is one method the body uses to “fight the induction of hypothermia. ” making it hard to lower body temperature enough.

“It’s great to see different cooling therapies being tested out for stroke because we know that physical cooling is just not feasible,” Coupland said.

The drug approach aims to avoid that human-scale problem. Promethazine and chlorpromazine act on the central nervous system to reduce core body temperature. without translating into shivering or subjective feelings of coldness. Promethazine is a sedating antihistamine that can ease hay fever and assist sleep. Chlorpromazine is an antipsychotic drug used in the management of schizophrenia and bipolar disorder.

But promising animal results don’t automatically survive the first test in people—and in the early clinical trial, the numbers were sobering.

After the animal work, the team conducted a clinical trial involving 32 people who had just had a stroke. On hospital admission. the subjects were given the promethazine and chlorpromazine combination or a placebo. on top of standard clot-removal therapy. In the patients. the promethazine and chlorpromazine treatment only reduced body temperature by 0.3°C (about 0.5°F) and did not reduce stroke damage.

Xuaili Xu. at Capital Medical University in Beijing. China. and his colleagues believed the dosing speed was the key failure point. He argued that the infusions were done over 12 hours. which was too slow to bring down core body temperature by a meaningful amount. In his view, that timing may have produced a low blood drug concentration per unit of time.

Now the research team is moving on quickly, launching another trial to test whether faster infusions over an hour can generate stronger cooling effects and better outcomes for patients.

Coupland pointed to the practical advantage the strategy already has: these are drugs used in humans for other indications. “The fact that they’ve proven that it’s safe and these drugs are already used in humans for other indications means I think that it’s reasonable to proceed with further clinical trials. ” she said.

The human stakes remain high. A stroke can leave lasting damage. and even when treatment restores blood flow. the early minutes can determine how much injury takes hold. The new effort is essentially a bet on timing—whether drug-driven cooling can reach the brain’s most vulnerable moment. without the shivering and discomfort that have derailed physical cooling attempts.

The next trial will show whether speeding up the infusion can turn a modest 0.3°C drop into something clinically meaningful—and whether “chilling” the body can truly soften the blow to the brain.

stroke brain damage hypothermia promethazine chlorpromazine drug cooling clinical trial clot removal glucose metabolism