On the specificity of naloxone as an opiate antagonist

Sawynok, Jana; Pinsky, Carl M.; LaBella, Frank S.

doi:10.1016/0024-3205(79)90403-x

Cited by 637 publications

(151 citation statements)

References 91 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…In additional experiments performed at the end of the study in seven normal subjects (25 to 30 years old), who were in similar clinical and experimental conditions as those previously described, the effect of ethanol + naloxone on OT levels was tested in the absence of insulin. This test was performed as the previously described ethanol + naloxone (4 + 10 mg) + ITT, except for the administration of normal saline instead of insulin.…”

Section: Erhunol+ Nuloxonr Testmentioning

confidence: 99%

Endogenous Opioids Modulate the Oxytocin Response to Insulin‐Induced Hypoglycaemia and Partially Mediate the Inhibitory Effect of Ethanol in Man

Coiro

Capretti²,

Davoli

et al. 1991

J Neuroendocrinology

View full text Add to dashboard Cite

The possible inhibition exerted by ethanol on the oxytocin (OT) response to insulin-induced hypoglycaernia was tested in man. Furthermore, the possibilities that endogenous opioids play a role in the control of hypoglycaemia andlor ethanol action on OT were examined. Insulin tolerance tests were performed in three groups of eight age-and weight-matched normal men treated with: 1) naloxone, group 1 1 mg bolus naloxonef2.5 mg over 105 min, group 2 2 mg bolus naloxone+5 mg over 105 min, group 3 4 rng bolus naloxone+ 10 mg over 105 min; 2) ethanol (50 ml in 110 ml of whiskey) to all the groups; 3) a combination of ethanol + naloxone; 4) normal saline. Furthermore, the effect of ethanol + naloxone (4f 10 mg) in the absence of insulin-induced hypoglycaemia was evaluated in seven additional subjects. During this latter test, the plasma levels of OT remained unchanged. Insulin-induced hypoglycaemia produced a 2.2-fold increment in plasma OT levels in the control experiments. This response was not changed by the treatment with the lowest dose of naloxone (1 +2.5 mg) in group 1, but it was significantly enhanced by administration of naloxone at higher doses (mean peak OT levels rose 2.8-fold in both group 2 and group 3). In all subjects the OT response to hypoglycaemia was completely abolished by ethanol. However, when ethanol was given together with naloxone, the hypoglycaemia-induced OT rise was only partially inhibited by ethanol. At all doses naloxone produced similar effects; in fact, in all groups OT rose 1.5-fold in response to hypoglycaemia during insulin tolerance test + ethanol + naloxone. Neither naloxone nor ethanol altered the basal secretion of OT, as tested during 45 min before the insulin tolerance test.These data demonstrate that the OT response to insulin-induced hypoglycaemia is inhibited by ethanol. Furthermore, the data indicate that endogenous opioids are involved in the control of hypoglycaemia-stimulated OT secretion and partially modulate ethanol inhibitory action.Ethanol is a well known inhibitor of oxytocin (OT) release in various animal species. In Fact, ethanol given in vivo reduced uterine contractions in parturient rabbits (I), lactating rabbits (2) and women (3) and almost completely inhibited milk production in rats (4). Furthermore, in vitro studies showed inhibition by ethanol of O T production from the isolated hypothalamo-hypophyseal system of the rat (5).Even though ethanol has been used for many years in the treatment of premature labour in women (6), experimental studies of ethanol action on OT secretion in humans are very scant.Insulin-induced hypoglycaemia has been shown to stimulate OT release in humans (7); therefore we wondered whether ethanol could inhibit hypoglycaemia-induced OT release. In addition, a variety of studies have shown a n inhibitory role of endogenous opioids on OT release (8) and an opioid mediation of ethanol action at various levels in the CNS (9). In view of these observations, we wondered whether the possible inhibitory effect of ethanol on OT migh...

show abstract

Section: Erhunol+ Nuloxonr Testmentioning

confidence: 99%

Endogenous Opioids Modulate the Oxytocin Response to Insulin‐Induced Hypoglycaemia and Partially Mediate the Inhibitory Effect of Ethanol in Man

Coiro

Capretti²,

Davoli

et al. 1991

J Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…More recently, it was suggested that morphinomimetic peptides could play an important inhibitory role in central control of blood pressure (Laubie, Schmitt, Vincent & Remond, 1977;Feldberg & Wei, 1978;Freye & Arndt, 1978;Bolme, Fuxe, Agnati, Bradley & Smythies, 1978; Arndt & Freye 1979b;Bellet, Elghozi, Meyer, Pernollet & Schmitt, 1980) or sympathetic tone (Farsang & Kunos, 1979). However, it is generally accepted that the opiate antagonist naloxone (Sawynok, Pinsky & Labella, 1979) alone does not affect blood pressure or heart rate (Farsang & Junos, 1979), although cardiovascular effects of nalone have been described in intact animals, especially at very high doses: Feria, Armijo, Mediavilla & Florez (1975) found that naloxone (at doses up to 3 mg/kg i.v.) induced a dose-dependent hypotensive response in rats anaesthetized with thiopentone plus urethane, whereas Feria, Boada & Alvarez (1980) have shown that naloxone (5 mg/kgi.v.)…”

Section: Introductionmentioning

confidence: 99%

Potentiation by Naloxone of Pressor Reflexes

Montastruc

Morales‐Olivas

1981

British J Pharmacology

View full text Add to dashboard Cite

1 The effect of intravenous naloxone, an opiate antagonist, was studied on the pressor responses elicited by stimulation of afferent nerves (vagus and laryngeal superior nerves) in anaesthetized dogs.2 Although naloxone (0.1 mg/kg i.v.) alone failed to modify basic blood pressure, the pressor responses induced by stimulation of either the vagus or laryngeal nerve were potentiated by naloxone.3 Morphine (0.2mg/kgi.v.) suppressed these two cardiovascular responses. These depressor effects of morphine were reversed by subsequent injection of naloxone (0.1 mg/kg i.v.). 4 The results suggest the involvement of endogenous opiate peptides in pressor reflexes elicited by stimulation of the afferent nerves. IntroductionBrain neurotransmitters and especially monoamines have been implicated in the mechanism of experimental arterial hypertension (Chalmers, 1975;Haeusler, 1976). More recently, it was suggested that morphinomimetic peptides could play an important inhibitory role in central control of blood pressure (Laubie, Schmitt, Vincent & Remond, 1977;Feldberg & Wei, 1978;Freye & Arndt, 1978;Bolme, Fuxe, Agnati, Bradley & Smythies, 1978;Arndt & Freye 1979b; Bellet, Elghozi, Meyer, Pernollet & Schmitt, 1980) or sympathetic tone (Farsang & Kunos, 1979 (Korner, 1971;Paintal, 1973;Sato & Schmidt, 1973) clonidine (Montastruc, Montastruc & Moatti, 1978a;Montastruc, Montastruc, Moatti & Mauco, 1978b). Methods AnimalsEleven dogs of either sex (mean weight 17.6 kg) were used. Before the experiments they were kept in the animal room maintained at a temperature of 19 ± 1°C and were fed a dry commercial food (U.A.R. Villemoison sur Orge, France) once daily at 09 h 00 min. Drinking water was always available. All experiments were done between 08 h 30 min and 12 h 00 min. Pressor responses to afferent nervous stimulationThe dogs were anaesthetized with urethane (1 g/kg i.v.). The trachea was intubated, the dogs were curarized (gallamine, 2 mg/kg i.v.) and artificially respired with an Ideal Palmer Pump. As in previous experiments (Laporte & Montastruc, 1957;Baisset, Laporte & Montastruc 1959;Baisset & Montastruc, 1964) urethane was chosen because it increased vascular reactions (especially pressor responses to nervous stimulation), and gallamine prevented the variations of the carotid arterial pressure induced by respiratory irregularities without inducing ganglioplegy (Laporte & Montastruc, 1957 (Korner, 1971;Paintal 1973;Sato & Schmidt, 1973).In a first series of experiments (experiment I), afferent stimulation was performed before (basic conditions) and 15 and 60 min after administration of naloxone. In another series of experiments (experiment II), the effects of morphine on pressor response to nervous stimulation were studied. Afferent stimulation was performed before (basic conditions) and 15 min after morphine. Laubie et al. (1977) and Laubie, Schmitt & Vincent (1979). Measurement of blood pressure Statistical evaluationsStatistical analysis was performed using Student's t test for paired comparisons. When the P value was ...

show abstract

“…While naloxone antagonism is regarded as a necessary criterion for opiate interaction, this alone is not sufficient to infer a narcotic mechanism (Sawynok, Pinsky & LaBella, 1979). By way of support for an opiate action in anaesthetically induced analgesia, Berkowitz, Finck, Hynes & Ngai (1979) have shown partial cross tolerance between nitrous oxide and morphine in rats.…”

Section: In Vitro Experimentsmentioning

confidence: 99%

Opiate‐like Analgesic Activity in General Anaesthetics

Lawrence¹,

Livingston²

1981

British J Pharmacology

View full text Add to dashboard Cite

1 The interaction of naloxone with various anaesthetics was studied both in vivo and in vitro.2 Naloxone (10mg/kg) did not significantly alter the anaesthetic duration of halothane, diethylether, ketamine, pentobarbitone or Althesin.3 Naloxone (10 mg/kg) reduced the analgesic activity of nitrous oxide, ketamine and morphine in the rat tail-flick test. With the exception of pentobarbitone and Althesin, the other anaesthetic agents also induced analgesia but were not antagonized by naloxone. (IC50 = 40 nM). 6 On the stimulated guinea-pig ileum, Met-enkephalin and morphine inhibited the contractions, the IC50 values were 30 nm and 50 nm respectively. The anaesthetics ketamine (IC50 = 10 FM) and Althesin (IC50=8,UM) were active. Xylazine (IC50=12nM) exhibited considerable potency in inhibiting the contractions on this preparation. Naloxone 0.5 p.M produced a 1000 fold shift in the opiate dose-response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone. 7 The activity of Althesin was found to be due to the vehicle in which this anaesthetic is solubilised.8 Whilst several anaesthetic agents showed analgesic activity, specific dihydromorphine binding displacement or guinea pig ileum inhibiting activity, these effects showed variable sensitivity to naloxone.

show abstract

On the specificity of naloxone as an opiate antagonist

Cited by 637 publications

References 91 publications

Endogenous Opioids Modulate the Oxytocin Response to Insulin‐Induced Hypoglycaemia and Partially Mediate the Inhibitory Effect of Ethanol in Man

Endogenous Opioids Modulate the Oxytocin Response to Insulin‐Induced Hypoglycaemia and Partially Mediate the Inhibitory Effect of Ethanol in Man

Potentiation by Naloxone of Pressor Reflexes

Opiate‐like Analgesic Activity in General Anaesthetics

Contact Info

Product

Resources

About