Why Agonist/Antagonist Drug Combinations Work

At the most fundamental level, the reason that adding an antagonist to an agonist in a specific ratio greatly reduces or eliminates receptor desensitization is that the dynamic competition between the agonist and the antagonist allows the receptor to function with little or no desensitization. What this means is that by slightly inhibiting the receptor, we can make sure that it doesn’t become overly excited and desensitized by the agonist drug alone.

What’s unique about this is that we can calculate the optimal ratios of agonist and antagonist to create the effects we want from the stimulated receptors. This hasn’t been accomplished before, because the importance of the agonist/antagonist ratio on receptor desensitization has gone unnoticed. Although there is some initial progress is this area, especially by Richard Bond (see - http://tinyurl.com/5kexhe, http://tinyurl.com/66oce8, http://tinyurl.com/6yhvgv and http://tinyurl.com/6plywh), the idea that we can create useful agonist/antagonist combinations to reduce or prevent desensitization, tachyphylaxis or tolerance has been slow to enter current pharmacological thinking.

This may seem surprising since our patented and published works were the first to describe how to make and control such agonist/antagonist combinations to achieve desired effects such as reducing or preventing receptor desensitization (see - http://tinyurl.com/6744mr, http://tinyurl.com/5ahxgm, http://tinyurl.com/5z8an6 and http://tinyurl.com/5mpsf7). Although this body of work has been ignored by many subsequent researchers, our priority dates on our patent filings certify our claims to first to discover this important means of modification of the receptor response.