This positive charge increases polarity and decreases lipid solubility when compared to traditional opioid agonists used for pain treatment.

[citation needed] The most common side effects for methylnaltrexone include:[8][10] In 1978, a dying friend and colleague presented the late University of Chicago pharmacologist Leon Goldberg with a clinical challenge.

Screening these compounds led to the examination of putative antagonists which when modified had properties that suggested they might not readily cross the blood–brain barrier based on their size and charge.

[14] The compound looked promising and passed initial screening in which rodents were given opioids along with charcoal meals to track GI transit, and were tested for analgesia.

[16] Subsequent preclinical studies also demonstrated this separation of central and peripherally mediated opioid effects for other smooth muscles of the GI tract and the cough reflex.

[21] In December 2005, Wyeth and Progenics entered into an exclusive, worldwide agreement for the joint development and commercialization of methylnaltrexone for the treatment of opioid-induced side effects, including constipation and post-operative ileus (POI), a prolonged dysfunction of the gastrointestinal tract following surgery.

Wyeth received worldwide rights to commercialize methylnaltrexone, and Progenics retained an option to co-promote the product in the United States.