naloxone and Drug-Hypersensitivity

Topics: Alfaxalone Alfadolone Mixture; Anesthesia, Intravenous; Drug Hypersensitivity; Etomidate; Humans; Mobile Health Units; Naloxone; Respiratory Insufficiency; Resuscitation

Topics: Aged; Analgesics, Opioid; Anaphylaxis; Drug Hypersensitivity; Female; Humans; Hydromorphone; Naloxone

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

The injection of morphine sulfate into baby mice twice daily for 5 days increased their running reaponse to morphine when they were tested as adults. If treatment was completed before the mice were )5 days old there was no effect. Sensitization to morphine running was longer-lasting than either analgesic tolerance or tolerance to morphine running may be a form of denervation hypersensitivity that has several features in common with noise-induced sensitization to audiogenic seizures.

Topics: Age Factors; Animals; Animals, Newborn; Cocaine; Cycloheximide; Dextroamphetamine; Dextrorphan; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Synergism; Female; Humans; Injections, Intraperitoneal; Injections, Subcutaneous; Levorphanol; Male; Mice; Mice, Inbred A; Mice, Inbred C57BL; Morphine; Motor Activity; Naloxone; Species Specificity; Substance-Related Disorders; Time Factors

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