Advances in opioid pharmacology

Abstract

Natural and synthetic opioid compounds, either alone or in combination with other drugs, are widely used analgesics for patients with both acute and chronic pain. Decades of extensive pharmacologic investigations have characterized three high-affinity cell-surface neuronal receptors, the activation of which is responsible for both the desirable properties (antinociception) and undesirable properties (respiratory depression, nausea and vomiting, dependence, etc.) of opioid drugs. Recent research in molecular biology and pharmacogenetics in relation to opioids and their receptors has helped clarify previous pharmacologic observations and has laid the groundwork for new analgesic therapies with improved therapeutic outcomes.

Deciphering the role of endogenous opioids in high-frequency TENS using low and high doses of naloxone

“…This is further confirmed by the index of effect size provided (see Results section). Evidence of a dose response relationship is also consistent with the idea that naloxone is a non-specific antagonistic which incrementally affects opioid receptors [11].…”

“…Sluka et al interpreted these findings as an indication that high and lowfrequency TENS analgesia were mediated by different opioid receptors, with lowfrequency TENS producing analgesia through μ opioid receptors and high-frequency TENS producing analgesia through δ opioid receptors. Indeed, the affinity of naloxone for δ opioid receptors is lower than that for μ opioid receptors [11], and it is likely that the inability to reverse high-frequency TENS analgesia in previous human studies [1;10;13;14;17;24;29] be attributable to the fact that the doses used were insufficient to antagonize the δ opioid receptors. Unfortunately, no human studies followed the work of Sluka and colleagues and it was impossible, until today, to confirm that high-frequency Animal evidence already support such a hypothesis, with studies showing (i) that animals rendered tolerant to high and low-frequency TENS are tolerant to δ and μ opioid agonists, respectively [6], and (ii) that rats tolerant to morphine are also tolerant to low-frequency TENS [26].…”

Neuropsychiatric pharmaceuticals and illicit drugs in wastewater treatment plants: a review

“…[21] Opioids can be classified into two categories: natural and synthetic. Natural opioids (opiates) are the naturally occurring alkaloids found in opium poppy plants (Papaver somniferum).…”

“…[15] Although drugs are usually detected in surface waters at only trace levels (ng L À1 to mg L À1 ), they are of increasing concern owing to their continual introduction into the environment, development of drug resistance in pathogenic organisms, and chronic toxicity including potential for synergistic effects in non-target organisms. [13,[16][17][18][19][20][21][22][23] Wastewater treatment plants are an important source for the introduction of pharmaceuticals into the environment. Drugs enter the treatment plants directly through disposal into the sewage system and, indirectly, as human excretion products where they are present both as free and conjugated forms (e.g.…”

Pharmacogenetics and the concept of individualized medicine

“…Studies of polymorphisms in the mu opioid receptors and transporter genes have contributed significantly to the knowledge of genetic influence on opioid and cocaine addiction and the efficacy of opioid therapy in pain management. [49][50][51][52] Environmental factors Environment-genotype interactions play a major role in drug therapy. For instance, inter-individual variability has been seen in human liver UDP-glucuronosyltransferase 1A6 (UGT1A6) enzyme activity that glucuronidates various drugs and toxins (Table 1).…”