Research by a Dignity Health St. Joseph's Hospital and Medical Center scientist on the development of novel painkillers without adverse effects on body temperature was recently published in the journal Acta Physiologica.
The research was conducted by St. Joseph's researcher Andrej A. Romanovsky, MD, PhD, and his team in collaboration with scientists at AbbVie, Amgen, and the medical school at the University of Pécs.
Blockers of the so-called TRPV1 channel are being developed as novel painkillers by several pharmaceutical companies. This development, however, has been hindered by adverse effects on body temperature - some TRPV1 blockers increase body temperature causing hyperthermia whereas others decrease it causing hypothermia.
This international team of academic scientists and pharma researchers found that the different adverse effects on body temperature stem from the same mechanism. If this mechanism is tamed, the drug will not affect body temperature in either direction.
For more than 10 years, Dr. Romanovsky's laboratory has studied TRPV1 blockers, synthesized by different pharmaceutical companies, each having a different effect on body temperature. Until now, scientists thought that different effects of TRPV1 blockers on body temperature were caused by different mechanisms. To their surprise, the present study showed that the hyperthermic and hypothermic effects are in fact caused through a reverse modulation of the exact same mechanism.
"The TRPV1 channel can be activated by different agents," explains Dr. Romanovsky, "but only one type of channel activation affects what will happen to the body temperature. It is the activation by an acidic environment. If an antagonist blocks this activation, hyperthermia occurs; if it exaggerates it, then hypothermia develops."
This discovery paves the way for creating new TRPV1 blockers with no side effects. In order to have no temperature effects, the new compounds should not interfere with TRPV1 activation by an acidic environment.
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Journal
Acta Psychologica