Pharmacology of Opioid Drugs

Abstract

Extracts of the opium poppy have been used for the relief of pain since antiquity. The active principle, morphine, continues to this day to be one of the most effective ways of alleviating moderate and severe pain. It is also one of the most addicting drugs known to man. This chapter describes the history of research on opium and the pharmacologic properties of morphine and related drugs. It briefly summarizes critical studies in the development of current knowledge of their antinociceptive actions; their effects on arousal, respiration, locomotor activity, and behavioral reinforcement; endocrine effects; and actions on peripheral tissues including the gastrointestinal tract, the genital tract, and the heart and circulatory system. The last section provides an overview of the absorption, metabolism, and distribution of morphine and other major opiate drugs.

Mu Opioids and Their Receptors: Evolution of a Concept

“…Although the hallmark of opiate pharmacology is its in vivo pharmacology, bioassays have played a major role in defining these drugs (Cox, 2011). The guinea pig ileum contraction assay was first described over 50 years ago (Schaumann, 1955;Kosterlitz and Robinson, 1957a;Paton, 1957).…”

“…Full descriptions of these are beyond the scope of this review, and readers are referred to a number of reviews (Cicero, 1980;Reisine and Pasternak, 1996;Pattinson, 2008;Diego et al, 2009Diego et al, , 2011Cox, 2011;Elliott et al, 2011;Wald, 2012). However, it is worthwhile to highlight several aspects of these additional functions.…”

Misuse of Novel Synthetic Opioids: A Deadly New Trend

“…For opioid drugs, the demonstration of pain relief (i.e., antinociception) in laboratory animals is usually indicative of analgesic actions in man (Cox, 2011). With respect to the NSO discussed here, estimating effective drug doses in humans based on animal studies presents significant challenges because: (1) various opioid drugs have been tested using diverse antinociception assay methods that are not always comparable; (2) drugs have been administered via different routes of administration or in different species across studies; (3) there is significant variability in antinociceptive dose-effect curves even among different strains of the same species (Elmer et al, 1998).…”

Functional relevance of μ–δ opioid receptor heteromerization: A Role in novel signaling and implications for the treatment of addiction disorders: From a symposium on new concepts in mu-opioid pharmacology

“…As discussed previously, μ and δ opioid receptors are coupled to Gα i proteins, and, upon activation, inhibit adenylyl cyclase in a pertussis toxin sensitive manner (Cox, 2010). Interestingly, these authors not only demonstrated that deltorphin-II may represent a potentially selective agonist of the μ-δ heteromer, but through [ 35 S]GTPγS assays, that μ-δ heteromer signaling is coupled to the pertussis toxin insensitive Gα z (Kabli et al, 2010).…”

“…All three opioid receptors are coupled to G i/o proteins, inhibit adenylyl cyclase and cAMP activity in vivo , and are functionally sensitive to pertussis toxin (Cox, 2010). As with other members of this class of receptors, the opioid receptors have been shown to undergo both homo- and heterotypic interactions in heterologous cell lines (Jordan and Devi, 1999; George et al, 2000; Gomes et al, 2000).…”