Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption. 2018

Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
School of Pharmacy, Pharmacology Unit, University of Camerino, Italy.

Buprenorphine's clinical use is approved for the treatment of heroin addiction; however, evidence supporting its efficacy in cocaine abuse also exists. While for heroin it has been demonstrated that the effect of buprenorphine is mediated by its ability to activate μ-opioid peptide receptor (MOP) receptors, the mechanism through which it attenuates cocaine intake remains elusive. We explored this mechanism using operant models where rodents were trained to chronically self-administer cocaine for 2 hours daily. Buprenorphine (0.3, 1.0 and 3.0 mg/kg) given intraperitoneally 90 minutes before access to cocaine significantly and dose dependently reduced its intake. Pre-treatment with naltrexone or with the selective nociceptin/orphanin FQ peptide (NOP) antagonist SB-612111 did not prevent buprenorphine-induced reduction of cocaine intake. However, when naltrexone and SB-612111 were combined, the effect of buprenorphine on cocaine was completely prevented. To confirm that co-activation of MOP and NOP receptors is the underlying mechanism through which buprenorphine reduces cocaine intake, three compounds, namely, AT-034, AT-201 and AT-202, with a range of affinity and intrinsic activity profiles for MOP and NOP receptors, but weak ability for kappa-opioid peptide receptor (KOP) transmission, were tested. Consistent with our hypothesis based on buprenorphine's effects, results demonstrated that AT-034 and AT-201, which co-activate MOP and NOP receptors, reduced cocaine self-administration like buprenorphine. AT-202, which selectively stimulates NOP receptors, was not effective. Together, these data demonstrate that for buprenorphine, co-activation of MOP and NOP receptors is essential to reduce cocaine consumption. These results open new vistas on the treatment of cocaine addiction by developing compounds with mixed MOP/NOP agonist properties.

UI MeSH Term Description Entries
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D010880 Piperidines A family of hexahydropyridines.
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D002047 Buprenorphine A derivative of the opioid alkaloid THEBAINE that is a more potent and longer lasting analgesic than MORPHINE. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. 6029-M,Buprenex,Buprenorphine Hydrochloride,Buprex,Prefin,RX-6029-M,Subutex,Temgesic,Temgésic,6029 M,6029M,Hydrochloride, Buprenorphine,RX 6029 M,RX6029M
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D003508 Cycloheptanes Seven-carbon cycloparaffin cycloheptane (the structural formula (CH2)7) and its derivatives.
D000094942 Nociceptin Receptor A member of the opioid subfamily of the G PROTEIN-COUPLED RECEPTORS. It is the receptor for the endogenous neuropeptide nociceptin. It functions in modulating NOCICEPTION and the perception of pain. KOR-3 Protein,Kappa3-Related Opioid Receptor,MOR-C Protein,Nociceptin Receptors,OFQ Receptor,OFQ Receptors,ORL1 Receptor,ORL1 Receptors,Opiate Receptor-Like 1,Opioid Receptor-Like Protein,Opioid-Receptor-Like 1 Protein,Orphanin FQ Receptor,Orphanin FQ Receptors,Receptor, Nociceptin,Receptor, OFQ,Receptor, Orphanin FQ,Receptors, ORL1,Noci-R,1 Protein, Opioid-Receptor-Like,1, Opiate Receptor-Like,FQ Receptor, Orphanin,FQ Receptors, Orphanin,MOR C Protein,Noci R,Opioid Receptor Like 1 Protein,Protein, KOR-3,Protein, MOR-C,Protein, Opioid Receptor-Like,Protein, Opioid-Receptor-Like 1,Receptor, Kappa3-Related Opioid,Receptor-Like 1, Opiate,Receptor-Like Protein, Opioid,Receptors, Nociceptin,Receptors, Orphanin FQ
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
February 2024, bioRxiv : the preprint server for biology,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
November 2003, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
January 2007, Biological psychiatry,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
September 2007, Biological psychiatry,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
February 2018, Neuropharmacology,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
January 2022, PloS one,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
January 2022, Journal of neuroscience research,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
October 2011, Journal of medicinal chemistry,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
May 2013, European journal of pharmacology,
Marsida Kallupi, and Qianwei Shen, and Giordano de Guglielmo, and Dennis Yasuda, and V Blair Journigan, and Nurulain T Zaveri, and Roberto Ciccocioppo
January 2015, Journal of addiction medicine,
Copied contents to your clipboard!