The combination of two medications commonly used to treat hay fever and psychosis has shown promising results in lowering core body temperature in animal models, subsequently reducing brain damage after a stroke. Early-stage trials in humans are currently underway to explore this innovative treatment further.

Over the years, researchers have focused on various cooling methods to protect the brain post-stroke. The goal is to induce a hibernation-like state in brain cells, minimizing their need for oxygen and glucose during a stroke when blood supply is compromised. Keeping brain cells viable until blood flow can be restored could help prevent extensive brain damage and potential long-term disabilities.

Traditional cooling methods, including cooling blankets and ice packs, have proven ineffective due to discomfort and uncontrollable shivering. According to Kirsten Cupland from the University of Newcastle, Australia, “Physical cooling often leads to severe discomfort, making it impractical. It’s encouraging to see alternative cooling therapies being researched for stroke treatment.”

Shivering is the body’s natural response to combat hypothermia, creating challenges in lowering body temperature effectively. “Understanding this limitation, I find the testing of alternative drugs for cooling therapy refreshing,” Coupland adds.

Research led by Shuaili Xu at Capital Medical University in Beijing tested promethazine and chlorpromazine, both established drugs known for their ability to reduce body temperature. This combination was administered to mice and rhesus macaques following induced strokes.

In both animal models, the drug combination successfully lowered core body temperature, decreased intracellular glucose metabolism, and significantly minimized brain damage caused by strokes. Notably, the treated monkeys exhibited improved limb functionality compared to untreated counterparts.

The research team subsequently conducted a trial involving 32 recent stroke patients who received either the drug combination or a placebo alongside standard clot-removal therapies.

Unfortunately, the combination therapy only produced a minor body temperature reduction of 0.3°C (approximately 0.5°F) without significant stroke damage reduction. Xu believes that the prolonged 12-hour infusion may have hindered the cooling process: “Faster admin could yield more substantial therapeutic effects,” he suggests.

His team is embarking on a new trial to investigate the potential of a rapid infusion method over one hour to enhance cooling effectiveness and therapeutic benefits. Coupland expressed optimism, noting, “The established safety profile of these drugs, already in human use for various conditions, supports the continuation of further clinical trials.”

Promethazine, a sedating antihistamine, alleviates hay fever and aids sleep, while chlorpromazine, an antipsychotic, treats schizophrenia and bipolar disorder. Both medications target the central nervous system to effectively lower core body temperature without causing shivering or cold sensations.