Designer Drugs: The Future Of Pain Medication

by Jennifer Wider, M.D.

(Washington DC 4/3/03):  The concept of personalized prescriptions, based on hair color, skin tone, and gender may seem far-fetched, but new research by Dr. Jeffrey Mogil, E.P. Taylor Professor of Pain Studies at McGill University in Montreal, and colleagues could potentially turn what sounds like science fiction into reality.

A team of researchers led by Dr. Mogil located a gene called the melanocortin-1 receptor gene or Mc1r, responsible for regulating pain relief from a class of drugs known as kappa-opioids. Human beings with red hair and fair skin have corresponding variations of the Mc1r gene. In experiments on mice, the researchers demonstrated that this gene controls kappa-opioid pain relief in females only. The researchers further proved that redheaded, fair-skinned women experienced better pain relief from pentazocine, a well-known kappa-opioid medication.

According to Dr. Mogil, the results of the study may allow doctors to base their prescriptions on inherited human traits in the future. "Our finding is an example of 'pharmacogenetics,' where genetic information can be used to predict drug response, and thus encourage individualized prescribing."

Not all women with red hair and fair skin have this genetic variation. "Allelic variants of the human Mc1r gene account for only 60-65% of red hair," according to Dr. Mogil. Therefore, not every woman with these physical characteristics will experience the same response to kappa-opioid medications. But the findings pave the way for more research to determine specific responses to medications based on genetic traits.

Previous studies have suggested that men and women actually use different brain mechanisms for pain relief. "We have shown (that) males and females appear to have distinct neural circuitry to modulate pain," Dr. Mogil explains, "[And] this information could result in the development of analgesic drugs that literally work in one sex but not the other."

In a 1999 randomized, double blind clinical trial, researchers at the University of California in San Francisco discovered that female patients achieved better pain control than male patients from kappa opioids after surgery to remove their wisdom teeth. At certain doses, the pain medication actually increased the pain for several male patients. In 2000, Australian researchers at the University of New South Wales showed in a randomized controlled trial that ibuprofen, the active ingredient in several over-the-counter medications, works more effectively in men.

The question of why women and men respond differently to certain medications has been a topic of study for years. While this research adds to a growing body of evidence about the role of the brain, other studies focus on hormones or social factors. It has been shown that a woman's pain threshold varies throughout her menstrual cycle, suggesting a potential role for estrogen and progesterone. In addition, some researchers have suggested that female perceptions about the effectiveness of medication may be enhanced because it is more socially acceptable for women to express their pain.

Doctors who have long been frustrated by the inconsistent response among their patients to prescription drugs may be encouraged by these findings pointing to the potential for future drugs to be tailored to their patients. As for headway that has already been made, the FDA approved a drug for irritable bowel syndrome in the summer of 2002, making it the first and only drug designed to alleviate constipation in female patients. As more research is conducted to determine the sex and genetic differences related to drug response, personalized medications have the potential to become readily available.

The Society for Women's Health Research is the nation's only not-for-profit organization whose sole mission is to improve the health of women through research. Founded in 1990, the Society brought to national attention the need for the appropriate inclusion of women in major medical research studies and the resulting need for more information about conditions affecting women. The Society advocates increased funding for research on women's health, encourages the study of sex differences that may affect the prevention, diagnosis and treatment of disease, and promotes the inclusion of women in medical research studies. Dr. Donnica Moore has been a member of the Society since 1990 and is a past member of its Board of Directors.

Created: 4/3/2003  -  Jennifer Wider, M.D.
Reviewed: 4/3/2003  -  Donnica Moore, M.D.