naloxone and Anaphylaxis

Topics: Adult; Anaphylaxis; Cardiac Tamponade; Cardiopulmonary Resuscitation; Emergency Medical Services; Fat Emulsions, Intravenous; Female; Heart Arrest; Humans; Hypothermia; Naloxone; Near Drowning; Percutaneous Coronary Intervention; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Water-Electrolyte Imbalance; Wounds and Injuries

The pathophysiological consequences of endorphin release in anaphylactic shock were investigated through pharmacological studies using opiate antagonists (naloxone, naltrexone, natrexone methyl bromide) as well as agonists (morphine, beta-endorphin). These studies suggest that induction of anaphylaxis provokes the release of endogenous opioids, possibly from the hypothalamus, which contribute to the shock process by stimulating opiate receptors in the CNS. The mechanism of pathophysiologic action of endorphin in anaphylaxis involves, at least in part, inhibition of the central component of the sympatho-adrenalmedullary system. This results in reduced effectiveness of the sympathetic system to physiologically reverse the circulatory effects of the toxic mediators of anaphylaxis. Naloxone, by blocking endorphin action at CNS opiate receptors located at autonomic regulatory centers (e.g. hypothalamus), reverses the sympatho-inhibitory effect of the endorphin peptides. This results in increased central sympathetic outflow to peripheral sympathetic neuroeffector mechanisms; it affords improved sympathetic compensatory responses and increases survival. TRH and DT gamma E physiologically oppose the action of endorphins upon the autonomic system. They stimulate central sympathetic mechanisms through their own receptor systems and increase outflow to peripheral sympathetic effectors. This also results in improved circulatory function and survival.

Topics: Anaphylaxis; Animals; Catecholamines; Endorphins; gamma-Endorphin; Mice; Naloxone; Receptors, Opioid; Sympathetic Nervous System; Thyrotropin-Releasing Hormone

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

Immediate hypersensitivity reactions in the intestinal mucosa evoke active chloride secretion which enhances the elimination of luminal antigens. The prosecretory actions of histamine and other soluble mediators of anaphylaxis are mediated by submucosal neurons, as are the antisecretory actions of opioid antidiarrheal medications. We tested the hypothesis that the selective delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) alters anaphylaxis-associated ileal anion secretion in vitro. Sheets of ileal mucosa with attached submucosa from guinea pigs sensitized to cow's milk were mounted in Ussing chambers under short-circuit conditions. Mucosal sheets responded to the serosal application of the milk protein, beta-lactoglobulin, with a rapid rise in transepithelial short-circuit current (Isc); in contrast, the egg protein, ovalbumin, was without effect. Pretreatment of tissues with the neuronal conduction blocker, saxitoxin, or the H1 histamine receptor antagonist, diphenhydramine, but not the opioid receptor antagonist, naloxone, significantly reduced mucosal responses to antigen. [D-Pen-2, D-Pen5]enkephalin (0.1 microM, serosal addition) decreased baseline Isc, but potentiated mucosal responses to antigen; its effects were abolished in tissues pretreated with naloxone. These results suggest that immediate hypersensitivity reactions in the guinea pig ileal mucosa are mediated by submucosal neural circuits that are phasically modulated by both mast cell products and opioids.

Topics: Analgesics; Anaphylaxis; Animals; Anti-Allergic Agents; Cricetinae; Diphenhydramine; Drug Interactions; Enkephalin, D-Penicillamine (2,5)-; Ileum; In Vitro Techniques; Lactoglobulins; Male; Milk; Mucous Membrane; Naloxone; Narcotic Antagonists; Ovalbumin; Saxitoxin

Following sensitization to ovalbumin (OA), male Wistar rats were pretreated with naloxone (20 mg/kg i.p.) and subjected to antigen challenge (3 mg OA i.p.). Naloxone exacerbated both systemic and intestinal anaphylaxis when injected 10 and 90 min before the antigen challenge. This was evidenced by a more pronounced drop in rectal temperature, higher hematocrit values, and by an enhanced elevation of basal short-circuit current (an indication of the secretory tone of the small intestine studied in Ussing chambers). Pretreatment with an equipotent does of methylnaloxone (200 mg/kg i.p.), a peripherally acting opiate antagonist, exacerbated the indices of intestinal anaphylaxis but had no apparent effect on indices of systemic anaphylaxis. Thus, our data strongly suggest that in the rat, components of the systemic hypersensitivity reaction are mediated through central opioid receptors, whereas the changes in gut function characterizing intestinal anaphylaxis are mediated through peripheral opioid receptors.

Topics: Anaphylaxis; Animals; Biological Transport; Cell Membrane Permeability; Chlorides; Hematocrit; Histamine Release; Hypothermia; Immunization; Intestinal Absorption; Male; Naloxone; Neuroimmunomodulation; Ovalbumin; Oxymorphone; Rats; Rats, Wistar; Receptors, Opioid; Specific Pathogen-Free Organisms; Water

Topics: Anaphylaxis; Animals; Body Temperature; Dose-Response Relationship, Drug; Female; Naloxone; Rats; Rats, Inbred Strains

1. It has been shown that opioid peptides modulate airway function. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea-pigs has been studied. 2. beta-Endorphin had a concentration-dependent bimodal effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (10(-10) and 10(-8) M) significantly potentiated anaphylactic contractions, whereas higher concentrations (10(-7) and 10(-6) M) significantly suppressed anaphylactic contractions of guinea-pig trachea. 3. beta-Endorphin in concentrations of 10(-8) M and 10(-7) M did not affect the responsiveness of the tracheal rings to histamine or leukotriene D4. This indicates that beta-endorphin does not influence the responsiveness of tracheal smooth muscle to anaphylactic mediators. 4. In the presence of the non-selective opioid receptor antagonist naloxone, 10(-8) M beta-endorphin still potentiated the anaphylactic contractions of the trachea. In addition, an equimolar concentration of des-Tyr1-beta-endorphin, a fragment of beta-endorphin without opioid-like activity, also potentiated anaphylactic contractions. The potentiation of anaphylactic contraction by 10(-8) M beta-endorphin is not therefore mediated by classical opioid-receptors. 5. In the presence of naloxone, 10(-7) M, beta-endorphin did not suppress anaphylactic contractions of the trachea. Thus, the suppression of anaphylactic contraction is mediated via a classical opioid-receptor. 6. In epithelium-denuded trachea, both 10(-8) and 10(-7) M beta-endorphin suppressed the anaphylactic contractions, whereas 10(-8) and 10(-7) M des-Tyr1-beta-endorphin did not affect anaphylactic contractions. It is concluded that the potentiation of the anaphylactic contraction in intact trachea is epithelium-dependent whereas the suppression of the anaphylactic contraction is epithelium-independent.

Topics: Anaphylaxis; Animals; beta-Endorphin; Epithelium; Guinea Pigs; Histamine; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Naloxone; Ovalbumin; Peptide Fragments; SRS-A; Trachea

It has been shown that opioid peptides induce histamine release and enhance antigen-induced histamine release from isolated peritoneal mast cells. Little is known about the effect of opioid peptides on mast cells present in airway smooth muscle. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea pigs was studied. It appears that beta-endorphin has a bidirectional effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (0.1 and 10 nM) significantly potentiate the anaphylactic contractions of tracheal rings. In contrast, higher concentrations of beta-endorphin (0.1 and 1 microM) significantly suppress the anaphylactic contractions of guinea pig trachea. In the presence of the non-selective opioid receptor antagonist naloxone, 10 nM of beta-endorphin still potentiates the anaphylactic contractions of the trachea. This demonstrates that the potentiation of anaphylactic contractions of guinea pig trachea by low concentrations of beta-endorphin is not mediated by opioid receptors. We speculate that the potentiation of the anaphylactic contraction by beta-endorphin is due to an interaction with mast cells.

Topics: Anaphylaxis; Animals; beta-Endorphin; Guinea Pigs; In Vitro Techniques; Male; Mast Cells; Muscle Contraction; Muscle, Smooth; Naloxone; Ovalbumin; Trachea

During the experiment conducted upon 85 guinea-pigs it has been found that the injection of naloxone at the dose of 0.5 g/kg half an hour before the reproduction of anaphylactic shock (AS) by the use of horse serum increases the number of cases of the retarded development of pathological reaction and survival of the animals. Except for the quantitative differences mentioned any peculiarities characterizing the effect of naloxone were not found. As to the morphological differences of variants in the course of AS they are distinctly defined only at the analysis of film preparations of the intestinal mesentery. The typical AS becomes apparent by haemorrhages, by dilatation of all the vessels of blood circulation and by forming of erythrocytic aggregates in them. At the retarded development of AS a spasm of precapillaries is observed. After convalescence of the animals the aggregates of erythrocytes can be revealed only in venules. Studying the animals recovered after AS one can find that for a long time these animals had the erythrocytic aggregates in the clearances of venules, as well as the signs of new formation of the capillaries.

Topics: Anaphylaxis; Animals; Drug Evaluation, Preclinical; Guinea Pigs; Immunization; Mesenteric Arteries; Mesenteric Veins; Microcirculation; Naloxone; Time Factors

The effects of opioid agonists and antagonists were investigated on humoral immune mechanisms in mice and rats. Opioid agonists like morphine, Leu-enkephalin, and Met-enkephalin, enhanced antigen-induced histamine release from mixed peritoneal cells of rats in vitro; this enhancement was effectively antagonized by naloxone, an opioid antagonist. Naloxone, per se, decreased anaphylactic mortality in doses of 10 mg/kg, while it increased mortality in a dose of 1 mg/kg. Reduced IgE antibody titer, measured by passive cutaneous anaphylaxis, decreased hemagglutination titer to sheep red blood cells, blocked histamine release from mixed peritoneal cells of rats in vitro induced by antigen, but had no significant effect when histamine release was induced by compound 48/80. Thus, it appears that endogenous opioids are involved in humoral immune responses.

Topics: Anaphylaxis; Animals; Antibody Formation; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Histamine Release; Mice; Morphine; Naloxone; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Rats

Possible involvement of endogenous opioids in humoral immune responses has been explored in the experimental animals. Opioid agonists like morphine and leu-enkephalin significantly enhanced antigen-induced histamine release from the peritoneal mast cells of sensitised rats in vitro; this was effectively antagonised by naloxone. Naloxone itself inhibited antigen-induced histamine release. Animals were effectively protected against anaphylactic shock by naloxone which also antagonised morphine-induced increase in anaphylactic mortality. Naloxone reduced haemagglutination titre to sheep red blood cells and IgE antibody titre as measured by passive cutaneous anaphylaxis. Thus, endogenous opioids appear to be involved in the mediation of humoral immune responses. They seem to act at various steps in the immune mechanism viz (i) antibody production and (ii) release of mediators of hypersensitivity reactions.

Topics: Anaphylaxis; Animals; Antibody Formation; Endorphins; Enkephalin, Leucine; Female; Hemagglutination; Histamine Release; Immunity; Male; Mice; Morphine; Naloxone; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Strains

Topics: Adult; Anaphylaxis; Codeine; Female; Humans; Naloxone

The lethal role of platelet activating factor (PAF) in anaphylactic shock was examined in mice, using the specific PAF antagonist, CV-3988. CV-3988 (0.3-3 mg/kg i.v.), given 5 min before PAF, protected mice from death (ED50, 0.9 mg/kg). CV-3988 (3 mg/kg i.v.), given 1 min after PAF was injected, was also effective, but no so effective when given 5 min later. Dexamethasone (2 mg/kg i.v. 3 hr before the PAF-injection), naloxone (1 and 10 mg/kg i.v. 5 min before), FPL-55712 (10 mg/kg i.v. 5 min before) and BW-755c (300 mg/kg p.o. 1 hr before) also improved the survival rate, but aspirin (100 mg/kg p.o. 1 hr before) did not. In anaphylactic shock, CV-3988 (0.3-3 mg/kg i.v.), given 5 min before and 5 min after rechallenge with antigen protected the sensitized mice from death (ED50, 1.2 and 0.48 mg/kg, respectively). Dexamethasone and naloxone protected mice from anaphylactic shock, but BW-755c and FPL-55712 had no protective effects. In contrast to CV-3988, dexamethasone and naloxone were ineffective when given 5 min after the rechallenge. Congestion of the lung, kidney and heart and infiltration of neutrophils in the lung were marked in mice with PAF-induced and anaphylactic shock. The related histology showed an improvement with CV-3988. These results strongly suggest that PAF may play a lethal role in anaphylactic shock and that CV-3988 may be an effective preventing agent.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Anaphylaxis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chromones; Dexamethasone; Male; Mice; Mice, Inbred Strains; Naloxone; Phospholipid Ethers; Platelet Activating Factor; Pyrazoles; SRS-A; Thiazoles

BALB/c mice and Wistar rats immunized with sheep red blood cells and ovalbumin were treated intraperitoneally with different doses of methionine-enkephalin, leucine-enkephalin, and naloxone. Large doses of enkephalins (10-5 mg/kg b.w.) induced a significant decrease in hemolysin-forming cell response and production of hemagglutinating antibody. Immunosuppression induced by enkephalin was dose-dependent. In rats met-enkephalin was a more potent immunosuppressor than leu-enkephalin. Rats injected with 2.5 mg/kg b.w. of enkephalins into the lateral ventricle of the brain showed more pronounced immune suppression than did animals treated intraperitoneally with 5 mg/kg b.w. of enkephalins. These neuropeptides, and met-enkephalin in particular, exhibited a protective action against anaphylactic shock in rats sensitized to ovalbumin. In those animals, passive cutaneous anaphylaxis and elaboration of precipitating anti-ovalbumin antibody were considerably reduced. On the other hand, small doses of enkephalins stimulated humoral immune responses in the rat. Thus, it appears that enkephalins both suppress and potentiate immune responsiveness, depending on the dose used. As for naloxone, a large dose of this blocker of opioid receptors enhanced humoral immune reactions in the rat.

Topics: Adjuvants, Immunologic; Anaphylaxis; Animals; Antibody Formation; Enkephalin, Leucine; Enkephalin, Methionine; Hemolytic Plaque Technique; Immunosuppression Therapy; Male; Mice; Mice, Inbred BALB C; Naloxone; Rats; Rats, Inbred Strains

Recent reports suggest that endorphins may contribute to hemodynamic depression in septic and hemorrhagic shock. There is also evidence that reversal of endorphin effects with high dose naloxone may improve hemodynamic function and improve survival in shock states. The purpose of this study was to examine the effects of naloxone on hemodynamic parameters in anaphylactic shock. Anaphylactic shock was induced in sensitized rabbits with horse serum. Three minutes after serum challenge, rabbits were treated with a 3 mg/kg bolus of naloxone followed by a 3 mg/kg per h infusion (group I, n = 8), or by injection with an equal volume of saline (group II, n = 8). Cardiac output, blood pressure, heart rate and body temperature were monitored continuously for 60 min and the experiment was terminated. There was a significant increase in cardiac index in group I animals at 10 min (P less than 0.01) and 15 min (P less than 0.01). Stroke volume index was also higher in naloxone treated animals at 10 min and 15 min (P less than 0.05). Although mean blood pressure was higher in group I animals at all time intervals after naloxone was begun, the difference was statistically significant only at 60 min (P less than 0.05). Peripheral vascular resistance index was not significantly different for the two groups.

Topics: Anaphylaxis; Animals; Blood Pressure; Cardiac Output; Female; Heart Rate; Male; Naloxone; Rabbits; Stroke Volume

Topics: Acupuncture Therapy; Anaphylaxis; Animals; Electric Stimulation Therapy; Female; Male; Mice; Mice, Inbred ICR; Naloxone; Phentolamine; Propranolol

Central injection of naloxone attenuated the development of hyperglycemia following induction of non-fatal anaphylaxis in mice, but it failed to reverse the hyperglycemia in this model. In contrast, central TRH both blocked as well as reversed the hyperglycemic response. These results suggest a possible role for central endorphin mechanisms in the hyperglycemic response to anaphylactic shock in mice. Further, they demonstrate a novel action of TRH to block shock-induced hyperglycemia. This antihyperglycemic action of TRH is independent of opiate mechanisms.

Topics: Anaphylaxis; Animals; Blood Glucose; Cerebral Ventricles; Endorphins; Homeostasis; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Naloxone; Thyrotropin-Releasing Hormone

The effect of naloxone on a number of experimental shock models, using the anaesthetized rat, was studied with special emphasis on mean arterial blood pressure (MABP) and chance of survival. Only a slight increase in MABP was noted in haemorrhagic shock models whereas survival was not affected. Naloxone was without effect in endotoxin shock (i.p. administration of endotoxin). In endotoxin shock (i.v. administration) naloxone increased MABP especially at a high dose of endotoxin. Although survival time was prolonged, the chance of permanent survival was not improved. Naloxone had practically no effect in anaphylactic shock and intestinal ischaemia shock. It is concluded that if naloxone has any effect it is relatively slight. However, this does not exclude the possibility that naloxone might still be considered as an adjunct to other forms of shock treatment at least in certain types of shock.

Topics: Anaphylaxis; Animals; Blood Pressure; Female; Intestines; Ischemia; Male; Naloxone; Rats; Rats, Inbred Strains; Shock; Shock, Hemorrhagic; Shock, Septic; Time Factors

gamma-Endorphin-type peptides (i.e. gamma-endorphin, des-tyr'-gamma-endorphin [DT gamma E]) result from the processing of the opioid peptide, beta-endorphin. Previous studies have implicated the involvement of beta-endorphin in various types of shock, including anaphylactic shock. In the present experiments the intracerebroventricular (i.c.v.) administration of gamma-endorphin (10 micrograms) or DT gamma E (3.3-10 micrograms) significantly improved survival in anaphylactic shock in mice. Moreover, DT gamma E (10 micrograms) reversed the effect of i.c.v. beta-endorphin (3.3 micrograms) to exacerbate shock. A similar dose of DT gamma E was ineffective in antagonizing beta-endorphin-induced analgesia. The anti-anaphylactic action of DT gamma E as well as its effect to block the pro-anaphylactic action of beta-endorphin were prevented by pretreatment with the sympathetic ganglionic blocker, chlorisondamine chloride. The results suggest that gamma-endorphin-type peptides may act in the central nervous system (CNS) to physiologically oppose the autonomic pathophysiologic influences of beta-endorphin.

Topics: Anaphylaxis; Animals; beta-Endorphin; Chlorisondamine; Drug Interactions; Endorphins; gamma-Endorphin; Male; Mice; Mice, Inbred ICR; Naloxone; Peptide Fragments; Serum Albumin, Bovine; Sympathetic Nervous System

Anaphylaxis results from the generation and release of a variety of mediators and their effects on various organs. Involvement of the respiratory and cardiovascular systems is of primary importance to the attending physician. Prompt recognition and initial therapy directed to maintenance of an effective airway and circulatory system is critical. Cardiovascular collapse may involve the parallel operation of several mechanisms including hypovolemia, alterations in pulmonary or systemic vascular resistance, depressed myocardial contractility, dysrhythmias, and exogenous drug administration. Although epinephrine is the mainstay of therapy, improvement in cardiovascular status may require aggressive fluid administration, and additional pharmacologic and non-pharmacologic aids.

Topics: Anaphylaxis; Blood Pressure; Epinephrine; Fluid Therapy; Gravity Suits; Histamine H1 Antagonists; Humans; Hypotension; Naloxone

Our recent studies indicated that there was a good therapeutic effect selecting acupoints "Renzhong (Du26 =G.V. 26)" "Chengjiang (Ren. 24=C.V.24) of electro-acupuncture (E-A) in the treatment of allergic shock induced by bovine serum in mice. Phentolamine or propranolol injection before needling could partially reverse this anti-allergic shock effect, while practolol had no influence on the effect of E-A in the treatment. Another series of experiments showed that the E-A anti-allergic shock effect could not be blocked by Naloxone or previous exhaustion of pituitary endorphins, thus suggesting that there might be a difference between mechanisms underlying the analgesic effect and those underlying the anti-allergic shock effect of acupuncture.

Topics: Acupuncture Therapy; Anaphylaxis; Animals; Electric Stimulation; Female; Male; Mice; Mice, Inbred Strains; Naloxone; Phentolamine; Practolol; Propranolol

The actions of meptazinol, pentazocine, morphine and naloxone on the cardiovascular changes accompanying anaphylactic shock were evaluated in ovalbumin-sensitized anaesthetized rats. Pretreatment with meptazinol and pentazocine prevented the fall in mean arterial pressure associated with antigen challenge, whereas morphine and naloxone attenuated but did not completely prevent, this change. None of the drugs significantly altered the antigen-induced decreases in heart rate. All the drugs partially reversed the fall in mean arterial pressure when given after antigen challenge although the activity of naloxone was less marked. Pretreatment with reserpine prevented the restoration of blood pressure by all drugs. Additional experiments with meptazinol showed that pretreatment with phentolamine prevented its pressor action. In pithed non-sensitized rats the frequency-pressor response curve to splanchnic stimulation was shifted to the left by meptazinol and shifted to the right by pentazocine, but the changes were small Morphine and naloxone had no significant effects. It was concluded that opioid mixed agonist-antagonists reverse the cardiovascular changes associated with anaphylactic shock. These effects appear to be mediated by facilitation of sympathetic neurotransmission.

Topics: Anaphylaxis; Animals; Azepines; Blood Pressure; Decerebrate State; Electric Stimulation; Female; Heart Rate; Hemodynamics; Meptazinol; Morphine; Naloxone; Pentazocine; Phentolamine; Rats; Rats, Inbred Strains; Reserpine; Time Factors

Intracerebroventricular (i.c.v.) administration of 10 micrograms naloxone significantly improved survival following experimental anaphylaxis in mice. The protective effect of i.c.v. naloxone was reversed by treatments which disrupted sympathetic outflow to the adrenal medulla, i.e. ganglionic blockade by chorisondamine chloride or denervation of the adrenal glands or by inhibition of beta-adrenoceptive sites by propranolol. These results indicate that naloxone's beneficial effect in anaphylactic shock involves central actions which are peripherally mediated through activation of beta-adrenoceptive mechanisms.

Topics: Adrenal Medulla; Anaphylaxis; Animals; Chlorisondamine; Denervation; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Naloxone; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Sympathetic Nervous System

When vascular access is delayed or unreliable in emergency situations, an endotracheal tube provides a rapid and reliable route for administration of medication. Epinephrine, lidocaine, and atropine have shown clinical efficacy when given by the endotracheal route. There is evidence that other medications including naloxone and diazepam may also be suitable for endotracheal use, but clear-cut recommendations await further studies of pharmacokinetics and toxicity.

Topics: Adult; Anaphylaxis; Anti-Arrhythmia Agents; Atropine; Bicarbonates; Diazepam; Emergencies; Epinephrine; Heart Arrest; Humans; Intubation, Intratracheal; Lidocaine; Naloxone; Pharmaceutical Preparations; Sodium Bicarbonate

Systemic anaphylaxis in the mouse is associated with marked hypoactivity. This effect is reversed by treatment with the opiate antagonists, naloxone (5-10 mg/kg) or naltrexone (1 mg/kg). Administration of naltrexone methyl bromide (1 mg/kg), a selective peripherally acting opiate antagonist, is ineffective in reversing the hypoactivity induced by anaphylaxis. These results suggest a role for central nervous system opiate mechanisms in the hypoactivity induced by anaphylaxis. They support the hypothesis that endogenous opiates contribute to the pathophysiologic consequences of anaphylactic shock.

Topics: Anaphylaxis; Animals; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Motor Activity; Naloxone; Naltrexone; Narcotic Antagonists

Topics: Anaphylaxis; Dextrans; Humans; Hypotension; Male; Middle Aged; Naloxone

Intravenous (i.v.) administration of 25 mg/kg morphine significantly increased mortality following induction of systemic anaphylaxis in mice. This effect was blocked by pretreatment with the opiate antagonist naltrexone but not by the selective peripherally acting antagonist naltrexone methyl bromide. Additionally, the effect of i.v. morphine was blocked by the opiate antagonist Win 44,441-3, but not by its inactive (+)-isomer Win 44,441-2. Furthermore, intracerebroventricular (i.c.v.) administration of 25 micrograms morphine increased anaphylactic mortality. This effect was blocked by i.v. naloxone. Finally, the effect of i.v. morphine, 25 mg/kg, on anaphylactic mortality was reversed by i.c.v. naloxone. Collectively, these findings demonstrate that morphine can exacerbate anaphylactic shock reactivity by stimulating specific CNS opiate receptors. The role of endogenous opiate mechanisms in the pathogenic sequence of circulatory shock is discussed.

Topics: Anaphylaxis; Animals; Azocines; Male; Mice; Mice, Inbred ICR; Morphine; Naloxone; Naltrexone; Receptors, Opioid

Topics: Anaphylaxis; Animals; Blood Pressure; Endorphins; Guinea Pigs; Male; Naloxone; Ovalbumin; SRS-A; Thyrotropin-Releasing Hormone; Time Factors

Intravenous naloxone, 1 or 10 mg/kg, protects sensitized mice from lethal anaphylaxis. The protective effect is reversed by pretreatment with the ganglionic blocker, chlorisondamine chloride, peripheral chemical sympathectomy with 6-hydroxydopamine or bilateral adrenal gland denervation. The possible involvement of the sympathetic nervous system in naloxone's antianaphylactic action, suggested by these findings, is discussed.

Topics: Adrenal Medulla; Anaphylaxis; Animals; Chlorisondamine; Hydroxydopamines; Male; Mice; Naloxone; Oxidopamine; Sympathetic Nervous System