piperidines and ibudilast

Topics: Animals; Cerebral Infarction; Humans; Nicergoline; Piperidines; Pyridines; Vasodilator Agents

Topics: Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic Disease; Humans; Nicergoline; Piperidines; Pyridines; Vasodilator Agents

Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil.. Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C).. A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone.. Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.

Topics: Administration, Inhalation; Analgesics, Opioid; Anesthetics, Inhalation; Animals; Behavior, Animal; Drug Interactions; Drug Tolerance; Injections, Intraperitoneal; Injections, Intravenous; Male; Methyl Ethers; Naloxone; Narcotic Antagonists; Pain Threshold; Piperidines; Pyridines; Rats, Wistar; Remifentanil; Sevoflurane; Time Factors; Toll-Like Receptor 4

Topics: Animals; Antibodies, Monoclonal, Humanized; Antigens, CD20; Azetidines; B-Lymphocytes; Benzamides; Benzyl Compounds; Blood-Brain Barrier; Clinical Trials as Topic; Disease Progression; Dogs; Drug Approval; Fingolimod Hydrochloride; Hope; Humans; Male; Mice; Multiple Sclerosis, Chronic Progressive; Neuroprotective Agents; Piperidines; Precision Medicine; Pyridines; Rituximab; Thiazoles; Ubiquinone; United States; United States Food and Drug Administration

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents; Constipation; Humans; Naltrexone; Narcotic Antagonists; Pain; Piperidines; Pyridines; Quaternary Ammonium Compounds; Receptors, Opioid, mu

Effects of 2-methyl-3-piperidino-beta-propionaphtone hydrochloride (KZ-111), 3-isobutyryl-2-isopropylpyrazolo-[1, 5-a]pyridine (KC-404) and FPL-55712 on experimental allergic reactions were investigated. Homologous passive cutaneous anaphylaxis (PCA) in rats was clearly inhibited by oral and intravenous administrations of KC-404 and KZ-111. FPL-55712 inhibited the PCA reaction only by intravenous injections, but not by oral administration. Maximum inhibition of the PCA reaction by KC-404 and KZ-111 was obtained by administration of these agents 2 hr prior to challenge. The immunological release of histamine from sensitized rat peritoneal mast cells was inhibited by KZ-111 at a concentration of 10(-4) g/ml. KC-404 and FPL-55712 did not inhibit the immunological release of histamine. All three compounds had no effect on the release of histamine from rat peritoneal mast cells and on the generation of SRS from rat polymorphonuclear leucocytes by calcium ionophore A23187. KC-404 and KZ-111 produced a downward displacement of the maximum without a parallel shift in LTD4 induced concentration-response curves of guinea pig ileal and tracheal smooth muscle at concentrations between 10(-6) and 10(-5) g/ml. FPL-55712 at a concentration of 10(-6) g/ml produced a parallel shift of LTD4 induced concentration-response curves to the right in both smooth muscle preparations. The 50% inhibitory concentration to the contraction by LTD4 of each of the three compounds is lower than those of other agonists, histamine, PGF2 alpha and BaCl2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Asthma; Chromones; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; Hypersensitivity; In Vitro Techniques; Male; Muscle Contraction; Passive Cutaneous Anaphylaxis; Piperidines; Pyridines; Rats; Rats, Inbred Strains; SRS-A