morphinans and Cocaine-Related-Disorders

morphinans has been researched along with Cocaine-Related-Disorders* in 2 studies

Other Studies

2 other study(ies) available for morphinans and Cocaine-Related-Disorders

Article	Year
Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior. ACS chemical neuroscience, 2015, Nov-18, Volume: 6, Issue:11 3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0.33 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors. Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50. However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay. Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction. Topics: Analgesics, Opioid; Animals; Cocaine; Cocaine-Related Disorders; Conditioning, Psychological; Dopamine Uptake Inhibitors; Drug Evaluation, Preclinical; Male; Mice, Inbred C57BL; Mice, Knockout; Molecular Structure; Morphinans; Naltrexone; Nociception; Nuclear Receptor Subfamily 1, Group F, Member 1; Random Allocation; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Reward; Spatial Behavior	2015
Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan. Bioorganic & medicinal chemistry letters, 2001, Oct-22, Volume: 11, Issue:20 A series of new N-substituted derivatives of morphinan was synthesized and their binding affinity for the three opioid receptors (mu, delta, and kappa) was determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-iodoprop-(2E)-enyl) (MCL-118) substituents on the binding affinities for the mu and kappa opioid receptors was observed. All of these novel derivatives showed a preference for the mu and kappa versus delta binding. Topics: Cocaine-Related Disorders; Drug Combinations; Humans; Morphinans; Narcotic Antagonists; Receptors, Opioid, kappa; Receptors, Opioid, mu	2001

Article

Year

Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.

ACS chemical neuroscience, 2015, Nov-18, Volume: 6, Issue:11

3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0.33 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors. Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50. However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay. Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction.

Topics: Analgesics, Opioid; Animals; Cocaine; Cocaine-Related Disorders; Conditioning, Psychological; Dopamine Uptake Inhibitors; Drug Evaluation, Preclinical; Male; Mice, Inbred C57BL; Mice, Knockout; Molecular Structure; Morphinans; Naltrexone; Nociception; Nuclear Receptor Subfamily 1, Group F, Member 1; Random Allocation; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Reward; Spatial Behavior

2015

Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan.

Bioorganic & medicinal chemistry letters, 2001, Oct-22, Volume: 11, Issue:20

A series of new N-substituted derivatives of morphinan was synthesized and their binding affinity for the three opioid receptors (mu, delta, and kappa) was determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-iodoprop-(2E)-enyl) (MCL-118) substituents on the binding affinities for the mu and kappa opioid receptors was observed. All of these novel derivatives showed a preference for the mu and kappa versus delta binding.

Topics: Cocaine-Related Disorders; Drug Combinations; Humans; Morphinans; Narcotic Antagonists; Receptors, Opioid, kappa; Receptors, Opioid, mu

2001