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Journal of Veterinary Pharmacology and... Feb 2013Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a...
Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability for 120 min, and the flux of methadone across the jejunal membrane (mucosal to submucosal direction) was calculated based on the relative drug concentration measured by ELISA. The flux of methadone was significantly higher only in the presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane of the jejunal epithelial cells (enterocytes), mainly located in the tip of the villi compared to cells of the crypts. P-glycoprotein is present in the equine jejunum and may possibly mediate the intestinal transport of methadone. This study suggests that P-glycoprotein may play a role in the poor intestinal absorption of methadone in vivo.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Analgesics, Opioid; Animals; Horses; Intestinal Absorption; Intestinal Mucosa; Jejunum; Methadone; Rhodamine 123; Verapamil
PubMed: 22428876
DOI: 10.1111/j.1365-2885.2012.01390.x -
Drug and Chemical Toxicology 1981d,1-Methadone hydrochloride was administered orally to adult female albino guinea pigs at a dose of 25 mg/kg body weight every 12 h for 10 consecutive days. Twelve hours...
d,1-Methadone hydrochloride was administered orally to adult female albino guinea pigs at a dose of 25 mg/kg body weight every 12 h for 10 consecutive days. Twelve hours after a dose, subgroups of animals were sacrificed at 2, 5 and 10 days for tissue (blood plasma, brain, liver and kidney) methadone residue analysis and the in vitro measurement of hepatic microsomal p-nitroanisole O-demethylase (OD), aniline hydroxylase (AH) and glucuronosyltransferase (GT) activities. No overt toxicity was observed during treatment other than a decrease in body weight. Withdrawal signs were absent during the 14-day post-treatment regression period. Tissue methadone levels were constant except for a decreased concentration in the liver at 5 and 10 days. No effect on hepatic OD and AH was observed during treatment but a significant decrease in GT activity was measured which returned to normal values 14 days after terminating treatment.
Topics: Animals; Body Weight; Female; Guinea Pigs; Liver; Methadone
PubMed: 7318686
DOI: 10.3109/01480548108998259 -
Journal of Neuroimmune Pharmacology :... Sep 2016Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy... (Review)
Review
Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy ((1)H MRS), and functional magnetic resonance imaging (fMRI), are powerful tools for assessing neurobiological mechanisms underlying the response to treatments in substance use disorders. Here, we review the neuroimaging literature on pharmacological and behavioral treatment in substance use disorder. We focus on neural effects of medications that reduce craving (e.g., naltrexone, bupropion hydrochloride, baclofen, methadone, varenicline) and that improve cognitive control (e.g., modafinil, N-acetylcysteine), of behavioral treatments for substance use disorders (e.g., cognitive bias modification training, virtual reality, motivational interventions) and neuromodulatory interventions such as neurofeedback and transcranial magnetic stimulation. A consistent finding for the effectiveness of therapeutic interventions identifies the improvement of executive control networks and the dampening of limbic activation, highlighting their values as targets for therapeutic interventions in substance use disorders.
Topics: Clinical Trials as Topic; Cognitive Behavioral Therapy; Craving; Humans; Methadone; Naltrexone; Neurofeedback; Neuroimaging; Substance-Related Disorders; Treatment Outcome
PubMed: 27184387
DOI: 10.1007/s11481-016-9680-y -
Pain Feb 1993Methadone is a synthetic opiate receptor agonist that has been available for more than 40 years. Although its main use has been in the maintenance treatment of opioid... (Review)
Review
Methadone is a synthetic opiate receptor agonist that has been available for more than 40 years. Although its main use has been in the maintenance treatment of opioid addicts, it has excellent analgesic effects and low cost. Its use is limited by its long and unpredictable half-life and by the limited knowledge of the most appropriate method for titration and interval of administration. Most reports on this drug are uncontrolled and limited to a small number of patients receiving low doses of methadone. Methadone should be titrated carefully and individualized doses and intervals should be determined for each patient. Future research should attempt to determine the equi-analgesic dose for chronic use, its effectiveness and tolerance when used in high doses, and its absorption and tolerance using alternative routes, e.g., rectal and subcutaneous.
Topics: Humans; Methadone; Neoplasms; Pain, Intractable
PubMed: 8455961
DOI: 10.1016/0304-3959(93)90125-9 -
The British Journal of Psychiatry : the... Nov 1983The authors conducted a preliminary trial of a 5-day course of diphenoxylate in the treatment of out-patients with methadone withdrawal symptoms. Diphenoxylate provided...
The authors conducted a preliminary trial of a 5-day course of diphenoxylate in the treatment of out-patients with methadone withdrawal symptoms. Diphenoxylate provided substantial relief from detoxification symptoms with no drug-associated adverse effects.
Topics: Adult; Diphenoxylate; Female; Humans; Isonipecotic Acids; Male; Methadone; Pilot Projects; Substance Withdrawal Syndrome
PubMed: 6640222
DOI: 10.1192/bjp.143.5.513 -
Current Pain and Headache Reports Feb 2009Although methadone is not a new medication, its use in pain management has increased rapidly over the past decade. This article reviews the unique pharmacologic... (Review)
Review
Although methadone is not a new medication, its use in pain management has increased rapidly over the past decade. This article reviews the unique pharmacologic properties of methadone, including its long-acting nature, highly variable clearance rate, and its antagonism of the N-methyl-D-aspartate receptor. We discuss potential benefits and risks of methadone over other opioid medications. Preclinical studies suggest methadone may reduce abuse potential, tolerance development, and sensitization of nociceptive pathways. Pharmacologic properties of methadone suggest potential greater risk of dangerous or fatal side effects from overdose, QT interval prolongation, and drug interactions. However, clinical studies have yet to confirm that methadone produces either better clinical outcomes or higher rates of adverse events than other opioid analgesics. Clinicians who understand the special properties of methadone and follow recommended precautionary prescribing and monitoring practices can safely and effectively use methadone for pain treatment.
Topics: Animals; Anti-Bacterial Agents; Drug Interactions; Humans; Methadone; Opioid-Related Disorders
PubMed: 19126367
DOI: 10.1007/s11916-009-0006-0 -
The Journal of Pharmacology and... Nov 1976Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after... (Comparative Study)
Comparative Study
Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after delivery. The newly born pups were divided into two groups. One group was tested for in vivo methadone tolerance, while the animals in the othergroup were used to prepare organotypic cerebellar cultures. Various amounts of dl-methadone were added to the media of half of these cerebellum cultures. The effect of the drug in the medium was assessed by measuring explant outgrowth. Similar experiments were carried out with control animals. Statistical analysis of the data obtained in the in vivo portion of the experiment indicates that the pups of methadone-treated mothers tolerate methadone better than those of untreated mothers. The culture experiments revealed that the addition of methadone to the medium reduced explant outgrowth size and this was a dose-related effect. Also, there was significantly less outgrowth from explants prepared using pups of methadone-treated mothers as compared to the controls. There was no significant difference in the effect of methadone on the growth of cultures prepared from the methadone-tolerant and control animals.
Topics: Animals; Animals, Newborn; Cells, Cultured; Cerebellum; Drug Tolerance; Female; Male; Maternal-Fetal Exchange; Methadone; Organ Culture Techniques; Pregnancy; Rats
PubMed: 978491
DOI: No ID Found -
Science (New York, N.Y.) May 1972
Topics: Drug and Narcotic Control; Heroin; Humans; Interpersonal Relations; Methadone; Social Behavior; Substance-Related Disorders; United States
PubMed: 5033630
DOI: 10.1126/science.176.4037.881 -
JAMA Oct 1972
Topics: Administration, Oral; Humans; Methadone; Substance-Related Disorders
PubMed: 4677843
DOI: No ID Found -
Clinical Pediatrics Jan 1974
Topics: Administration, Oral; Boston; Child; Child, Preschool; Drug Packaging; Female; Heroin Dependence; Humans; Infant; Male; Methadone; Naloxone; Poisoning; Respiration
PubMed: 4809614
DOI: 10.1177/000992287401300110