Opioid peptide receptor studies. 10. Nor-BNI differentially inhibits kappa receptor agonist-induced G-protein activation in the guinea pig caudate: Further evidence of kappa receptor heterogeneity

Heyliger, Simone O.; Jackson, C. M.; Rice, Kenner C.; Rothman, Richard B.

doi:10.1002/(sici)1098-2396(19991215)34:4<256::aid-syn2>3.0.co;2-6

Cited by 9 publications

(1 citation statement)

References 55 publications

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“…To date, only one KOPr receptor type (KOPr-1: KOPr) has been cloned. Although pharmacological data indicate the existence of multiple KOPr receptor subtypes (KOPr-1, KOPr-2, KOPr-3) (Heyliger et al, 1999;Horan et al, 1993), a clear demonstration of KOPr heterogeneity has proved elusive. A recent study (Olianas et al, 2006) has shown that the prototypic KOPr-3 agonist, naloxonebenzoylhydrazone, is a partial agonist at the cloned μ-(MOPr), δ-(DOPr), and KOPr as well as an antagonist at opioid-like nociceptin receptors.…”

Section: Physiology and Pharmacology Of Dyn/ Kopr Systemsmentioning

confidence: 99%

Dynorphin and the pathophysiology of drug addiction

Shippenberg¹,

Zapata²,

Chefer³

2007

Pharmacology & Therapeutics

324

348

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Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that may ensue. As drug use becomes more compulsive, motivation for natural rewards that normally drive behavior decreases. The discontinuation of drug use is associated with somatic signs of withdrawal, dysphoria, anxiety, and anhedonia. These consequences of drug use are thought to contribute to the maintenance of drug use and to the reinstatement of compulsive drug use that occurs during the early phase of abstinence. Even, however, after prolonged periods of abstinence, 80-90% of human addicts relapse to addiction, suggesting that repeated drug use produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response (habit) learning. A major goal of addiction research is the identification of the neural mechanisms by which drugs of abuse produce these effects. This article will review data showing that the dynorphin/kappa-opioid receptor (KOPr) system serves an essential function in opposing alterations in behavior and brain neurochemistry that occur as a consequence of repeated drug use and that aberrant activity of this system may not only contribute to the dysregulation of behavior that characterizes addiction but to individual differences in vulnerability to the pharmacological actions of cocaine and alcohol. We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/KOPr system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction.

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Section: Physiology and Pharmacology Of Dyn/ Kopr Systemsmentioning

confidence: 99%

Dynorphin and the pathophysiology of drug addiction

Shippenberg¹,

Zapata²,

Chefer³

2007

Pharmacology & Therapeutics

324

348

View full text Add to dashboard Cite

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Salvinorin A Analogs and Other Kappa-Opioid Receptor Compounds as Treatments for Cocaine Abuse

Kivell

Ewald

Prisinzano

2014

Advances in Pharmacology

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Acute activation of κ opioid receptors produces anti-addictive effects by regulating dopamine levels in the brain. Unfortunately, classic κ opioid agonists have undesired side effects such as sedation, aversion and depression which restrict their clinical use. Salvinorin A (Sal A), a novel κ opioid receptor agonist extracted from the plant Salvia divinorum, has been identified as a potential therapy for drug abuse and addiction. Here, we review the preclinical effects of Sal A in comparison with traditional κ opioid agonists and several new analogues. Sal A retains the anti-addictive properties of traditional κ opioid receptors agonists with several improvements including reduced side effects. However, the rapid metabolism of Sal A makes it undesirable for clinical development. In an effort to improve the pharmacokinetics and tolerability of this compound, κ opioid receptor agonists based on the structure of Sal A have been synthesized. While work in this field is still in progress, several analogues with improved pharmacokinetic profiles have been shown to have anti-addiction effects. While in its infancy, it is clear that these compounds hold promise for the future development of anti-addiction therapeutics.

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