Enhanced Pharmaceuticals, GPCRs, Drug Safety

At Enhanced Pharmaceuticals, we’ve discovered that the rather simple act of combining an agonist with the proper amount of an antagonist allows for a general decrease in the observed drug-receptor desensitization, tachyphylaxis or tolerance. This modulation of the receptor response appears to be a quite general phenomenon applicable to many G Protein-Coupled Receptors (GPCRs), but because it is an unexpected result that differs from most pharmacological theories and clinical intuition, it hasn’t caught on in the last 16 years since the filing of my first patent on September 30, 1992. Although it was previously reported for the opioid and nicotinic receptors, no other research group has characterized and defined their experimental results using predictive biophysical and pharmacodynamic models as we have.

Although at least three companies including Enhanced Pharmaceuticals were formed around such findings, general pharmacological science has been rather slow to follow up on these findings. Truthfully, this puzzles me, because these findings represent a paradigm shift in the pharmacology field toward discovering and making safer and more effective drugs. Big pharma appears to be looking in all the wrong places to extend their patent franchises while ignoring or remaining unaware of technologies such as ours to improve their drugs.

There remains more experimental work to do, but from our studies it appears that these agonist/antagonist drug combinations work well in animals that desensitize differently and that they appear to work after desensitizing a targeted receptor system such as for the Guinea-pig trachea (an accepted experimental system for asthma studies). In our animal studies, there were also less cardiac arrhythmias with our drug combinations than with the agonist (activating) drugs alone. These studies are promising, but need further research. Because our work holds such promise for better asthma, heart failure and Parkinson drugs, we continue to hope that investors will see our potential and rise to the opportunities.

Richard G. Lanzara, M.P.H., Ph.D.
President Enhanced Pharmaceuticals, Inc.