morphinans and Drug-Hypersensitivity

Increased demands for potable water, especially where supplies are drawn from lowland rivers has necessitated a greater degree of water re-use. As water undertakings have a duty to maintain the wholesome quality of potable water supplies, increasing concern is being expressed over the presence of organic micro-contaminants (contaminants found at microgram litre-1 concentrations). This study outlines some of the problems encountered in assessing the risk from pharmaceutical chemicals which might enter the water cycle from domestic and industrial sources. Analytical chemistry was of value for only a few of the 200 compounds studied. However, much useful information was derived from the human metabolic routes of the drugs and is collated in Appendix I. Biodegradation studies and other ecotoxicity/environmental toxicology data may be required to a greater extent in the future. Particular consideration is given to vulnerable sections of the population.

Topics: Antineoplastic Agents; Drug Hypersensitivity; Drug Interactions; Enzymes; Female; Gas Chromatography-Mass Spectrometry; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Morphinans; Pharmaceutical Preparations; Pregnancy; Renal Dialysis; Sewage; Water Pollutants; Water Pollutants, Chemical; Water Supply

Mast cells are vital mediators of drug allergy and, therefore, studying the relationship between drug allergy and mast cells is essential. Sinomenine is the principal active component of Sinomenium acutum, which has anti-inflammatory and anti-immune effects, and is used to treat various rheumatoid diseases. However, allergic responses to sinomenine are frequently reported. Therefore, this study assessed the effects of sinomenine on mast cell activation to characterize its allergic effects and the underlying mechanisms. Enzyme-linked immunosorbent assay (ELISA), western blot analyses, and degranulation assays were performed to measure pro-inflammatory and allergic mediators in P815 cells. The allergenic effects of sinomenine were also determined in mice by using active general anaphylaxis (ASA). The results indicated that sinomenine induced inositol-1,4,5-trisphosphate (IP

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Calcium; Cell Degranulation; Cell Line, Tumor; Drug Hypersensitivity; Inflammation; Inositol 1,4,5-Trisphosphate Receptors; Interleukin-6; Male; Mast Cells; Mice; Mice, Inbred BALB C; Morphinans; Phospholipase C gamma; Phosphorylation; Signal Transduction; src-Family Kinases; Up-Regulation

Sinomenine (SIN), an alkaloid derived from the Chinese medicinal plant Sinomenium acutum, is the major component of Zhengqing Fongtong Ning (ZQFTN), a pharmaceutical drug produced by Hunan Zhengqing Pharmaceutical Co. Ltd. in China for the treatment of rheumatoid arthritis and other autoimmune diseases. Some clinic reports indicate that ZQFTN may induce an anaphylactic reaction via potentiating the degranulation of immune cells. In the current study, we aimed to examine whether SIN is capable of inducing the degranulation of basophilic leukemia 2H3 (RBL-2H3) cells to elucidate how the anaphylactic reaction occurs. The results revealed that SIN could up-regulate β-hexosaminidase levels in RBL-2H3 cells without significant cytotoxicity, suggesting that SIN could induce the degranulation of RBL-2H3 cells. Furthermore, SIN increased the release of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) in RBL-2H3 cells via promoting the expression of phosphorylated-extracellular signal-regulated kinase (P-ERK), the cleavage of Annexin A1 (ANXA1), and phosphorylated-cytosolic phospholipase A2 (P-cPLA2), as well as cyclooxygenase-2 (COX-2). The ERK inhibitor, PD98059, significantly attenuated the up-regulatory effect of SIN on cPLA2 phosphorylation. Interestingly, SIN did not significantly increase Ca(2+) influx in the cells. These findings not only explored the anaphylactic reaction and underlying mechanism of ZQFTN in RBL-2H3 cells, but may promote the development of relevant strategies for overcoming the adverse effects of the drug.

Topics: Anaphylaxis; Animals; Annexin A1; Arthritis, Rheumatoid; Basophils; Calcium; Cell Degranulation; Cell Line; Drug Hypersensitivity; Humans; MAP Kinase Signaling System; Morphinans; Phospholipases A2; Phosphorylation; Rats; Sinomenium

Due to low central nervous system (CNS) bioavailability of delta-opioid peptides, little is known about the effect of systemic administration of delta-opioid receptor ligands. The present study examined the effect of non-peptidergic delta-opioid receptor agonists, (+)-4-[(alphaR)-alpha-((2R,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) and (-)dibenzoyl-L-tartaric acid salt (SNC86), on the activity of alpha-motoneurons in decerebrate-spinal rats. The flexor reflex was facilitated by C-afferent conditioning inputs, shown by a decrease in mechanical threshold and increase in touch- and pinch-evoked responses. Systemic administration of SNC80 (10 micromol/kg) prevented and reversed the neuronal hyperactivity. We further examined the effect of this agonist on the hypersensitivity of the flexor reflex induced by intraplantar injection of Freund's adjuvant. SNC80 dose-dependently (1, 3, 5 and 10 micromol/kg) increased the mechanical threshold and decreased touch-, pinch- and Abeta-afferent inputs-evoked responses. Similar effects were seen with SNC86 (5 micromol/kg). Pretreatment with either naloxone (20 micromol/kg, i.p.) or (Cyclopropylmethyl)-6,7-dehydro-4,5alpha-epoxy-14beta-ethoxy-5beta-methylindolo [2',3':6',7']morphinan-3-ol hydrochloride (SH378; 5 micromol/kg, intraarterially (i.a.)), a novel selective delta-opioid receptor antagonist, completely abolished the anti-hypersensitivity effect of SNC80. The effect of SNC80 remained following intrathecal administration of mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP; 1.5 nmol). These results indicate that systemic injection of SNC80 exerted antihypersensitivity in models of both acute and tonic nociception and these effects are mediated mainly through a spinal delta-opioid mechanism.

Topics: Afferent Pathways; Animals; Benzamides; Central Nervous System; Conditioning, Psychological; Dose-Response Relationship, Drug; Drug Hypersensitivity; Electric Stimulation; Electrophysiology; Freund's Adjuvant; Hindlimb; Indoles; Inflammation; Male; Morphinans; Motor Neurons; Naloxone; Narcotic Antagonists; Pain Measurement; Piperazines; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, mu; Reflex; Somatostatin; Tartrates; Touch

A case of opioid withdrawal precipitated in an opioid-dependent person by low plasma levels of naloxone is presented. In this patient, changes were observed in the hypothalamic-pituitary-adrenal (HPA) axis that preceded the clinical symptoms and adrenergic signs of withdrawal. Plasma naloxone levels were strongly correlated with plasma cortisol levels (P < .0001, R2 = .73, r = .85). In addition, these neuroendocrine changes persisted after adrenergic changes and clinical symptoms had been ameliorated by administration of a short-acting opioid agonist. It is suggested that the HPA axis is a more sensitive indicator of opioid withdrawal than the adrenergic system.

Topics: Drug Hypersensitivity; Female; Humans; Hypothalamo-Hypophyseal System; Middle Aged; Morphinans; Naloxone; Narcotic Antagonists; Pituitary-Adrenal System; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Buprenorphine; Drug Hypersensitivity; Epidural Space; Female; Humans; Injections; Morphinans

Topics: Drug Hypersensitivity; Female; Humans; Morphinans; Nalorphine; Naloxone

Topics: Adrenal Cortex Hormones; Agranulocytosis; Anti-Bacterial Agents; Ascorbic Acid; Blood Transfusion; Drug Hypersensitivity; gamma-Globulins; Humans; Morphinans