Prescription opioid formulations designed to resist or deter abuse are an important step in reducing opioid abuse. In creating these new formulations, the paradigm of drug development target should be introduced. Biological targets relating to the nature of addiction may pose insurmountable hurdles based on our current knowledge and technology, but products that use behavioral targets seem logical and feasible. The population of opioid abusers is large and diverse so behavioral targets are more challenging than they appear at first glance. Furthermore, we need to find ways to correlate behavioral observations of drug liking to actual use and abuse patterns. This may involve revisiting some pharmacodynamic concepts in light of drug effect rather than peak concentration. In this paper we present several new opioid analgesic agents designed to resist or deter abuse using physical barriers, the inclusion of an opioid agonist or antagonist, an aversive agent, and a prodrug formulation. Further, this paper also provides insight into the challenges facing drug discovery in this field. Designing and screening for opioids intended to resist or deter abuse is an important step to meet the public health challenge of burgeoning prescription opioid abuse. 1. Introduction A fundamental tenet and driving force of drug discovery is that there is a clear and important medical need for which we can identify a biological target. Success in drug discovery is measured insofar as this medical need is adequately addressed to the extent that our current understanding of basic science and existing technology permits. The biological target can take many forms. For example, in the case of a new angiotensin-converting enzyme (ACE) inhibitor for hypertension, there is both a clear medical need (essential hypertension) and an obvious biological target (inhibitor of the enzyme). A more complex example might be a new drug for the amelioration of symptoms of Alzheimer’s disease. The medical need for such a drug is clear, but the biological target may be only hypothetical. The justification for initiating drug discovery in this case is clear, even if the outcome is less so. Another example might be a novel insulin delivery system that provides insulin release in a manner that more closely matches blood glucose levels. In this example, the medical need is valid and the discovery target merges biological with technological principles. When it comes to designing and screening for opioids that deter abuse, the same principles should be applied, but formulators should be aware of medical
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