pyrimidinones and Pain

On the basis of the results of earlier published and recent examinations it could be concluded that among analgesics Probon is the first of choice especially in case of chronic pain accompanying chronic respiratory tract diseases. The value of the drug is also supported by the fact that the number of patients suffering from chronic obstructive respiratory failure increases continuously, since the equilibrium of these patients is very unstable; the smallest injury, such as an increase in secretion, a decrease in diaphragmatic movement, or chest expansion caused by pain, or even drug-induced respiration depression, may very easily upset this equilibrium.

Topics: Aged; Analgesics; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Pain; Pyrimidinones; Respiration; Respiratory Tract Diseases

Topics: Analgesics; Arthritis; Arthritis, Rheumatoid; Chemical Phenomena; Chemistry; Drug Therapy, Combination; Drug Tolerance; Gastrointestinal Hemorrhage; Humans; Indomethacin; Pain; Pyrimidinones

this study aimed to investigate the effect of antivirals ritonavir and lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral oxycodone, a widely used opioid receptor agonist used in the treatment of moderate to severe pain.. a randomized crossover study design with three phases at intervals of 4 weeks was conducted in 12 healthy volunteers. Ritonavir 300 mg, lopinavir/ritonavir 400/100 mg, or placebo b.i.d. for 4 days was given to the subjects. On day 3, 10 mg oxycodone hydrochloride was administered orally. Plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined for 48 h. Pharmacokinetic parameters were calculated with standard noncompartmental methods. Behavioral effects and experimental cold pain analgesia were assessed for 12 h. ANOVA for repeated measures was used for statistical analysis.. ritonavir and lopinavir/ritonavir increased the area under the plasma concentration-time curve of oral oxycodone by 3.0-fold (range 1.9- to 4.3-fold; P <0.001) and 2.6-fold (range 1.9- to 3.3-fold; P <0.001). The mean (± SD) elimination half-life increased after ritonavir and lopinavir/ritonavir from 3.6 ± 0.6 to 5.6 ± 0.9 h (P <0.001) and 5.7 ± 0.9 h (P <0.001), respectively. Both ritonavir (P <0.001) and lopinavir/ritonavir (P <0.05) increased the self-reported drug effect of oxycodone.. ritonavir and lopinavir/ritonavir greatly increase the plasma concentrations of oral oxycodone in healthy volunteers and enhance its effect. When oxycodone is used clinically in patients during ritonavir and lopinavir/ritonavir treatment, reductions in oxycodone dose may be needed to avoid opioid-related adverse effects.

Topics: Adult; Analgesics, Opioid; Area Under Curve; Cross-Over Studies; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Finland; HIV Infections; HIV Protease Inhibitors; Humans; Linear Models; Lopinavir; Male; Oxycodone; Pain; Pyrimidinones; Reference Values; Ritonavir; Time Factors; Young Adult

On the basis of the results of earlier published and recent examinations it could be concluded that among analgesics Probon is the first of choice especially in case of chronic pain accompanying chronic respiratory tract diseases. The value of the drug is also supported by the fact that the number of patients suffering from chronic obstructive respiratory failure increases continuously, since the equilibrium of these patients is very unstable; the smallest injury, such as an increase in secretion, a decrease in diaphragmatic movement, or chest expansion caused by pain, or even drug-induced respiration depression, may very easily upset this equilibrium.

Topics: Aged; Analgesics; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Pain; Pyrimidinones; Respiration; Respiratory Tract Diseases

Topics: Adult; Aged; Analgesics; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Pain; Pyrimidinones; Thoracic Surgery; Thorax

Topics: Adult; Aged; Analgesics; Carboxylic Acids; Clinical Trials as Topic; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Pain; Placebos; Pyrimidinones

Topics: Analgesics; Azo Compounds; Clinical Trials as Topic; Codeine; Humans; Naphthalenes; Pain; Placebos; Pyrimidinones

Topics: Aged; Analgesics; Arm; Aspirin; Carboxylic Acids; Clinical Trials as Topic; Codeine; Drug Synergism; Humans; Ischemia; Pain; Pyrimidinones

Topics: Analgesics; Antipyrine; Carboxylic Acids; Clinical Trials as Topic; Codeine; Humans; Methylamines; Pain; Placebos; Pyrimidinones; Sulfates; Sulfonic Acids

Topics: Glomus Tumor; Humans; Neurofibromatosis 1; Pain; Pyridones; Pyrimidinones

Topics: Drug Therapy, Combination; Endometriosis; Female; Humans; Pain; Phenylurea Compounds; Pyrimidinones

Topics: Female; Freedom; Humans; Leiomyoma; Pain; Phenylurea Compounds; Pyrimidinones; Randomized Controlled Trials as Topic; Uterine Neoplasms

Topics: Female; Gonadotropin-Releasing Hormone; Humans; Japan; Leiomyoma; Pain; Phenylurea Compounds; Pyrimidinones

TRPM8 has been implicated in pain and migraine based on dorsal root- and trigeminal ganglion-enriched expression, upregulation in preclinical models of pain, knockout mouse studies, and human genetics. Here, we evaluated the therapeutic potential in pain of AMG2850 ((R)-8-(4-(trifluoromethyl)phenyl)-N-((S)-1,1,1-trifluoropropan-2-yl)-5,6-dihydro-1,7-naphthyridine-7(8H)-carboxamide), a small molecule antagonist of TRPM8 by in vitro and in vivo characterization. AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %). When tested in a skin-nerve preparation, AMG2850 blocked menthol-induced action potentials but not mechanical activation in C fibers. AMG2850 exhibited significant target coverage in vivo in a TRPM8-mediated icilin-induced wet-dog shake (WDS) model in rats (at 10 mg/kg p.o.). However, AMG2850 did not produce a significant therapeutic effect in rat models of inflammatory mechanical hypersensitivity or neuropathic tactile allodynia at doses up to 100 mg/kg. The lack of efficacy suggests that either TRPM8 does not play a role in mediating pain in these models or that a higher level of target coverage is required. The potential of TRPM8 antagonists as migraine therapeutics is yet to be determined.

Topics: Action Potentials; Animals; Behavior, Animal; Blood Pressure; Brain; Calcium; CHO Cells; Cold Temperature; Cricetinae; Cricetulus; Freund's Adjuvant; Humans; Hyperalgesia; Male; Menthol; Mice, Inbred C57BL; Naphthyridines; Pain; Pyrimidinones; Rats; Rats, Sprague-Dawley; Sciatic Nerve; TRPM Cation Channels

Topics: Arteriosclerosis Obliterans; Female; Humans; Ischemia; Leg; Male; Middle Aged; Pain; Pyrimidinones

Topics: Analgesia; Analgesics; Carboxylic Acids; Humans; Kinins; Pain; Psychophysiologic Disorders; Pyrimidinones; Respiration

Topics: Aminopyrine; Amobarbital; Analgesics; Animals; Aspirin; Blood; Cats; Codeine; Diazepam; Dogs; Drug Antagonism; Drug Synergism; Glutethimide; Guinea Pigs; Haplorhini; Methods; Mice; Morphinans; Morphine; Naphthalenes; Pain; Phenacetin; Pyrimidinones; Rabbits; Rats; Synaptic Transmission

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Naphthalenes; Pain; Pyrimidinones; Rats

Topics: Analgesics; Carboxylic Acids; Drug Synergism; Evaluation Studies as Topic; Humans; Lung Neoplasms; Narcotics; Pain; Postoperative Care; Pyrimidinones; Rib Fractures; Thoracic Diseases; Thoracic Surgery; Thorax