dynorphins and nalmefene
dynorphins has been researched along with nalmefene* in 6 studies
Reviews
1 review(s) available for dynorphins and nalmefene
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[Place of the opioid system in biology and treatment of Alcohol Use Disorder].
While the DSM 5 has formalized the terminology "Alcohol Use Disorders" (AUD) or "disorders of the use of alcohol" (UAW French translation in progress), the term "alcohol dependence" still used in ICD-10, apriority in the future ICD-11 and above in clinical practice. Addiction to alcohol is the cause of mortality and major morbidity. In terms of therapeutic strategies for its management, alongside the maintenance of abstinence after withdrawal (with a high rate of relapse), the reduction of alcohol consumption below certain thresholds of intake is emerging in order to reduce risk, improve health and regain control of consumption even be an intermediate step towards abstinence. The role of the endogenous opioid system in the modulation of the activity of dopaminergic neurons from the circuit of reward and motivation is well established. An unsteadiness of this system has been described in the alcohol dependence. Indeed, a hypofunction of the endorphin pathway and its mu receptor and a hyperactivity of the dynorphin pathway and its kappa receptor participate in the alcohol reinforcing effects (especially positive and negative). The development of active molecules in this system allows better management of alcohol dependence. Besides naltrexone (mu antagonist) allowed in the maintenance of abstinence after withdrawal, another molecule (nalmefene) with modulating properties of μ and κ opioid receptors is the first drug having obtained an MA in reducing consumption in adult patients with alcohol dependence. Its modulating original pharmacological properties by targeting both the positive but also the negative reinforcing effects of alcohol, are responsible for its development in reducing consumption in the alcohol dependence. Topics: Alcoholism; Brain; Craving; Diagnostic and Statistical Manual of Mental Disorders; Dynorphins; Endorphins; Humans; International Classification of Diseases; Naltrexone; Neurotransmitter Agents; Receptors, Opioid | 2014 |
Trials
2 trial(s) available for dynorphins and nalmefene
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Cervene (Nalmefene) in acute ischemic stroke : final results of a phase III efficacy study. The Cervene Stroke Study Investigators.
The goals of the present study were to assess the efficacy and safety of nalmefene (Cervene) in patients with acute (< or =6 hours) ischemic stroke and to investigate the safety of combined recombinant tissue plasminogen activator and nalmefene in a separate subset of patients. Nalmefene, an opioid antagonist with relative kappa receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. Results from an earlier phase II study in patients with acute ischemic stroke suggested that nalmefene was safe and tolerable and may be effective for patients <70 years old.. This investigation was a phase III, placebo-controlled, double-blind, randomized study of a 24-hour infusion of nalmefene. Patients with acute ischemic stroke who had an onset of symptoms within 6 hours and a baseline score of > or =4 on the NIH Stroke Scale were randomized to receive either 60 mg nalmefene administered as a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75 hours or placebo. The primary efficacy outcome was the proportion of patients achieving a score of > or =60 on the Barthel Index and a rating of "moderate disability" or better on the Glasgow Outcome Scale at 12 weeks. Assessments were performed at baseline (predose), hours 12 and 24, days 2 and 7, and week 12.. A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old.. Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours. Topics: Acute Disease; Aged; Aged, 80 and over; Brain Ischemia; Dose-Response Relationship, Drug; Double-Blind Method; Dynorphins; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Nausea; Neuroprotective Agents; Receptors, Opioid, kappa; Risk Factors; Survival Analysis; Treatment Failure | 2000 |
Dynorphin A1-13 causes elevation of serum levels of prolactin through an opioid receptor mechanism in humans: gender differences and implications for modulation of dopaminergic tone in the treatment of addictions.
Dynorphin peptides act preferentially at kappa- as well as mu- and delta-opioid receptors. This study was conducted to determine whether dynorphin peptides act to lower dopaminergic tone in the tuberoinfundibular system, resulting in elevated serum prolactin levels and, if so, whether such an effect is mediated by the opioid receptors. Dose-related increases in serum prolactin levels were observed after dynorphin A1-13 was administered i.v. in doses of 120 and 500 micrograms/kg to healthy human volunteers with no history of drug or alcohol abuse. Studies were then conducted to determine whether this effect is opioid receptor mediated and, if so, whether at kappa- or mu types. Pretreatment with the opioid antagonist nalmefene (30 mg i.v.), which has high affinity at both mu- and kappa-opioid receptors, caused a greater attenuation in dynorphin A1-13-stimulated increases in serum prolactin levels than pretreatment with similarly high doses of naloxone, an antagonist with lower affinity for both mu- and kappa-opioid receptors. These results suggest dynorphin A1-13 lowers tuberoinfundibular dopaminergic tone through action at kappa- and possibly mu-opioid receptors. Female subjects were significantly more responsive to the prolactin effects of dynorphin than were male subjects. Dynorphin gene expression, dynorphin peptides, and kappa-opioid receptor gene expression and binding have been shown to be altered in response to cocaine administration. Also, both dynorphin peptides and synthetic kappa-opioid agonists have been shown to lower dopamine levels in the nucleus accumbens and to attenuate cocaine-induced surges in dopamine levels. Thus, a dynorphin-like compound capable of reaching critical mesolimbic-mesocortical and nigrostriatal dopaminergic systems may be effective in the management of cocaine addiction. Topics: Adult; Analgesics, Opioid; Analysis of Variance; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Dynorphins; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Narcotic Antagonists; Peptide Fragments; Prolactin; Receptors, Dopamine; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Sex Characteristics; Time Factors | 1999 |
Other Studies
3 other study(ies) available for dynorphins and nalmefene
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Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.
The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa (kappa)-opioid system has a role in the increased consumption of ethanol in dependent animals. The effects of three opioid receptor antagonists with different effects on opioid receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats. Nalmefene and naltrexone are both opioid receptor ligands with comparable molecular weights and pharmacokinetic profiles, but differing specificity for the three opioid receptor subtypes at low doses, while nor-BNI is a selective kappa-opioid receptor antagonist. Dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14 h per day. Subsequent to dependence induction, nalmefene, naltrexone, and nor-BNI were tested for their ability to modulate self-administration of ethanol in vapor-exposed and control rats. The results indicated that both nalmefene and naltrexone induced a significant dose-dependent decrease in the number of lever presses for ethanol in both groups of animals. However, in ethanol-dependent animals, nalmefene was significantly more effective in suppressing ethanol intake than naltrexone. Nor-BNI selectively attenuated ethanol-dependent self-administration while leaving nondependent ethanol self-administration intact. Because naltrexone is primarily selective for the mu-opioid receptor, and nalmefene is primarily selective for the mu- and kappa-opioid receptor subtypes, the fact that nalmefene demonstrates more suppression in dependent animals suggests that opioid systems distinct from the mu-regulated portion may be involved in the increased drinking seen during withdrawal in dependent animals. The results with nor-BNI confirm that kappa-opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/kappa-opioid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent rats. Topics: Administration, Inhalation; Alcoholism; Animals; Central Nervous System Depressants; Conditioning, Operant; Data Interpretation, Statistical; Dynorphins; Ethanol; Injections, Intraventricular; Male; Motivation; Naltrexone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Self Administration; Substance Withdrawal Syndrome | 2008 |
Inhibiting a spinal dynorphin A component enhances intrathecal morphine antinociception in mice.
Morphine given intracerebroventricularly releases spinal dynorphin A (Dyn) in mice. The present study was undertaken to determine whether morphine given intrathecally (IT) released Dyn. We demonstrated that the antinociceptive action of morphine was enhanced by procedures that are known to attenuate Dyn action. First, coadministration of the opiate antagonists, naloxone (5 fg), norbinaltorphimine (5 fg) or beta-funaltrexamine (0.25 ng) with IT morphine (0.15 microgram, 5 min) increased antinociceptive percentage maximum possible effect (%MPE) from 30% to 65%. Second, dynorphin antiserum (5 micrograms, 1 h, IT), which neutralizes Dyn action, enhanced morphine (0.2 microgram, 5 min, IT) action; MPE of 27% was increased to 60%. Third, production of desensitization to the antagonistic action of Dyn, IT, by pretreatment with morphine [10 mg/kg, 3 h, subcutaneously (SC)], or 2 micrograms, 3 h, IT) or Dyn (1 ng, 1 h, IT) increased the 30% MPE of IT morphine to 60%. Naloxone [1 ng/kg, intraperitoneally (IP)] enhanced IT morphine at a peak time of 20 min. Nalmefene [1 to 100 ng/kg, per os (PO)] enhanced IT morphine action. In conclusion, the present study showed that IT morphine putatively released spinal Dyn. Topics: Analgesics; Animals; Cerebral Ventricles; Dynorphins; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Spine | 1993 |
Dynorphin A-(1-17) induces alterations in free fatty acids, excitatory amino acids, and motor function through an opiate-receptor-mediated mechanism.
The endogenous opioid dynorphin A-(1-17) (Dyn A) has been implicated as a mediator of tissue damage after traumatic spinal cord injury (TSCI) and causes hindlimb paralysis when administered intrathecally. Motor impairment following intrathecal Dyn A is attenuated by antagonists of excitatory amino acids (EAAs); whether opioid receptors mediate such injury has been questioned. TSCI causes various biochemical changes associated with secondary tissue damage, including alterations in tissue amio acids, phospholipids, and fatty acids. Such changes reflect injury severity and correlate with motor dysfunction. The present studies examined whether dynorphin administration causes similar biochemical alterations and whether effects of Dyn A can be modified by treatment with opioid-receptor antagonists. At 24 hr after intrathecal Dyn A, there were significant declines in tissue levels of glutamate, aspartate, and glycine. Increases in total free fatty acids were found at 2 and 24 hr, reflecting changes in both saturated and unsaturated components, which were associated with significant decreases in tissue cholesterol and phospholipid phosphorus at the earlier time point. Each of these neurochemical changes, as well as corresponding motor deficits, were limited by pretreatment with the opioid antagonist nalmefene. In separate experiments, both nalmefene and the selective kappa-opioid antagonist nor-binaltorphimine (nor-BNI) limited dynorphin-induced motor dysfunction; effects of nor-BNI were dose related, and those of nalmefene were stereospecific. Therefore, behavioral and neurochemical consequences of Dyn A administration are mediated in part through opiate receptors, most likely kappa-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Amino Acids; Animals; Dose-Response Relationship, Drug; Drosophila Proteins; Dynorphins; Fatty Acids, Nonesterified; Injections, Spinal; Male; Membrane Proteins; Motor Activity; Naltrexone; Nerve Tissue Proteins; Peptide Fragments; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Spinal Cord; Spinal Cord Injuries; Stereoisomerism | 1990 |