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Biomedical subjects

R D Sewell

Publications and source records attributed to R D Sewell.

At least 55 records · Page 3Linked to original sources
PubMed1984

The involvement of mu- and kappa- but not delta-opioid receptors in the body weight gain of suckling rats.

The effects of the benzomorphan antagonist Mr 2266 and the selective delta-antagonist ICI 154,129 on the body weight gain of 6-day-old suckling rat pups was observed. Mr 2266 significantly reduced body weight gain in these animals, though ICI 154,129 had no affect on this variable. These findings suggest that mu- and kappa- but probably not delta-opioid receptors are involved in the regulation of ingestive behaviours in infant rats. The results are discussed in relation to the development of opioid-receptor subtypes in the neonatal rat brain.

Animals↗
PubMed1984

Meptazinol cross-tolerance studies between morphine or oxotremorine.

The time course of the development of auto-tolerance to meptazinol as determined by combined heat and pressure nociceptive tests has been examined using two dose levels of meptazinol (10 mg and 30 mgkg-1s.c.) corresponding to the partial agonist and cholinergic components respectively. In mice treated twice daily with meptazinol for eight days, there was cross tolerance to morphine in both tests at each dose level of meptazinol. In chronic morphine treated mice challenged with meptazinol (30 mg kg-1 s.c.), there was no cross tolerance with morphine since meptazinol still retained its antinociceptive effects in both tests. Mice treated chronically with meptazinol (30 mgkg-1 s.c.) did not respond to the cholinomimetic agent oxotremorine, implying that there was cross tolerance between these two analgesics. These data suggest the existence of a one-way tolerance between morphine and meptazinol whilst at higher doses of meptazinol a full tolerance occurs with oxotremorine.

Animals↗
PubMed1984

The role of opioid receptor sub-types in tifluadom-induced feeding.

There is now considerable evidence that opioid agonists and benzodiazepines increase food and water intake in a variety of animal species. The appetitive effects of the novel opioid-benzodiazepine tifluadom have been investigated. (+/-)-Tifluadom significantly increased food intake in freely-feeding rats. This stimulation of appetite was attributable principally to the activity of the (+)-isomer. Furthermore tifluadom-induced feeding was blocked by the opioid antagonists naloxone, naltrexone, Mr 1452 and Mr 2266 but not by the delta-opioid receptor antagonist ICI 154, 129, or by the benzodiazepine antagonist Ro 15-1788. These results suggest that tifluadom exerts its effect on food intake by interaction with opioid as opposed to benzodiazepine receptors and that this activity is mediated by kappa and/or mu- rather than delta-opioid receptor sub-types.

Animals↗
PubMed1984

Subacute benzodiazepine treatment: observations on behavioural tolerance and withdrawal.

The acute and subchronic actions of the benzodiazepines triazolam, oxazepam and diazepam have been examined using three behavioural tests. In the accelerating rotarod motor coordination test both diazepam and oxazepam on acute administration produced dose-related discoordination or motor impairment in mice. After chronic administration (50 mg/kg per day i.p. for 14 days) the corresponding dose-response lines were shifted to the right suggesting tolerance development. In a test for conflict behaviour in rats (conditioned suppression of drinking) oxazepam (20 mg/kg i.p.), triazolam (1 mg/kg i.p.) and diazepam (10 mg/kg i.p.) all augmented punished responding rates with no effect on unpunished responses and this has been speculated to reflect anxiolytic activity. These initial elevations in punished responding displayed a gradual decline during repeated daily administration over 20 days, there being little alteration in the unpunished response levels. In separate studies, chronic treatment of mice with triazolam in the drinking water over 30 days showed diminished pentylenetetrazol-induced seizure latencies compared to the level of protection afforded by triazolam at the beginning of the schedule. In additional experiments, mice injected daily with triazolam (1 mg/kg i.p. for 14 days) exhibited a higher seizure susceptibility than their corresponding controls. The results are discussed in relation to tolerance to the anxiolytic, anticonvulsant and neurological impairment properties of benzodiazepines.

Animals↗
PubMed1984

Meptazinol activity on morphine-naive and morphine-dependent guinea-pig ileum: correlation with in vivo studies.

The effects of meptazinol and some opioid agonists and antagonists were studied on opioid-naive guinea-pig ileum (GPIN) and ileum taken from morphine-dependent guinea-pigs (GPID). Meptazinol produced a biphasic effect in GPIN and GPID with a depression of the electrically induced twitch response at lower concentrations and contractural potentiation at higher concentrations. The effects of meptazinol in both GPIN and GPID were similar, thus distinguishing it from the other opioid agonists and antagonists which produced differential effects on these tissues. In morphine-pelletted rats, meptazinol (5 mg/kg i.p.) did not produce notable withdrawal as measured by behavioural observation. However, meptazinol (30 mg/kg i.p.) enhanced the signs associated with cholinergic activation. It is suggested that meptazinol possesses a cholinergic component and that the morphine-withdrawal signs observed to the higher meptazinol dose were more probably attributable to cholinergic stimulation rather than any underlying opioid-precipitated withdrawal.

Animals↗
PubMed1984

Comparison of the relative effects of aspirin, mefenamic acid, dihydrocodeine, dextropropoxyphene and paracetamol on visceral pain, respiratory rate and prostaglandin biosynthesis.

A comparison was made between the relative effects of aspirin, mefenamic acid, dihydrocodeine , dextropropoxyphene and paracetamol on visceral pain (chemically-inducing writhing), respiratory rate and prostaglandin (PG) biosynthesis (cyclo-oxygenase activity). A close correlation was found to exist between inhibition of PG biosynthesis and inhibition of visceral pain for mefenamic acid, aspirin and paracetamol. Analysis of the complete activity profiles derived from evaluation of the test parameters yielded the following rank order of overall ratios of their beneficial anti-writhing/anti-cyclo-oxygenase to respiratory depressive activities: (1) mefenamic acid, (2) aspirin, (3) dihydrocodeine , (4) dextropropoxyphene and paracetamol.

Acetaminophen↗
PubMed1983

Effects of elevated calcium and calcium antagonists on 6,7-benzomorphan-induced analgesia.

The hypothesis that the nociceptive state and opiate-induced antinociception are generally regulated by Ca2+ brain levels has been tested. In this context, the effects of intracerebroventricular injections of CaCl2 (0.1-0.5 mumol), D600 (5.0-10.0 micrograms) and EGTA (0.5-1.0 mumol) on ethylketocyclazocine (EKC), ketocyclazocine (KC), Mr-2033, pentazocine (PTC), bremazocine (BMC) and SKF 10,047-induced antinociception were investigated in the mouse tail immersion test. Simultaneous treatment with either D600 or EGTA resulted in a significant and dose-related enhancement in the activities of the kappa-agonists: EKC, KC and Mr-2033, whilst the activities of PTC, BMC and SKF 10,047 remained unchanged. CaCl2 readily blocked the activities of all benzomorphans tested except that of SKF 10,047 against which CaCl2 was less effective. In addition a dose-related hyperalgesia was observed when CaCl2 was given alone. Although the results obtained from the kappa-agonists and CaCl2 per se support the hypothesis in question, data obtained from PTC, BMC and SKF 10,047 tends to oppose it. Additionally the present results taken together indirectly substantiate the notion that benzomorphan-induced analgesia may involve different opiate-sensitive neuronal substrates.

Analgesia↗
PubMed1983

Differential effects of SKF 38393 and LY 141865 on nociception and morphine analgesia.

The effects of SKF 38393 and LY 141865 on nociceptive sensitivity and morphine-induced analgesia were compared. SKF 38393 administered to mice either peripherally or centrally was without effect on either base line response latencies or morphine's analgesia. By contrast, s.c. injections of LY 141865 resulted in a dose-related hyperalgesia. A paradoxical analgesia was observed when LY 141865 was given intracerebroventricularly. Both the analgesia and hyperalgesia were antagonized by sulpiride but remained unaffected by the opioid antagonist Mr-1452. Central and peripheral pretreatment with LY 141865 resulted in respective enhancement and attenuation in the analgesic activity of morphine. The present results would indicate that D-2 receptors may be involved in nociception and analgesic mechanisms. In addition it suggests that D-2 receptors may exert both inhibitory and facilitatory influences on nociceptive and analgesic mechanisms.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1983

Characterization of a kappa-agonist-like antinociceptive action of tifluadom.

The novel benzodiazepine tifluadom was compared with a selection of proposed mu- and kappa-opiate agonists using a combined heat/pressure nociceptive paradigm. Calculation of the relative potency ratios to the nociceptive stimuli revealed a distinction between mu- and kappa-agonists. The potency ratio yielded by tifluadom coincided with that displayed by the kappa-agonists and this finding is discussed in relation to morphine withdrawal and radioligand binding studies.

Analgesics↗
PubMed1983

Analgesic actions of mu- and kappa-opiate agonists in rats.

The antinociceptive profiles of mu- and kappa-opiate agonists were determined in a combined tail immersion plus tail pressure nociceptive test in rats. Combined analysis of potencies for pressure against heat noxia enabled differentiation between all mu- and kappa-agonists tested, thus confirming previous studies in other animal species and paralleling observations from studies on isolated tissue preparations. The distinct antinociceptive profiles produced by mu- and kappa-agonists provide further quantitative evidence that these agents are behaviourally different.

Analgesics, Opioid↗
PubMed1982

Differentiation of potent mu and kappa-opiate agonists using heat and pressure antinociceptive profiles and combined potency analysis.

The antinociceptive profiles of strong mu- and kappa-opiate agonists were determined in the tail clip, hot plate (55 degrees C) and tail immersion (48 degrees C and 55 degrees C) tests in mice. All mu- and kappa-agonists produced steep dose-response lines in all the tests. Using a combined analysis of potencies for pressure against heat noxia it was possible to differentiate between mu- and kappa-agonists and this paralleled findings in other laboratories using isolated tissue preparations. It was also concluded that qualitative rather than quantitative differences between noxia were responsible for the observed differentiation since potency differences for mu- and kappa-agonists between tests were maintained even after the intensity of heat and pressure noxia were equated. It was also proposed that use of the combined tail clip and immersion tests may be useful for rapid behavioural classification of novel synthetic mu- and kappa-opiate analgesics.

Analgesics, Opioid↗
PubMed1982

Stereospecific inhibition of oxotremorine-induced antinociception by (+)-isomers of opioid antagonists: comparison with opioid receptor agonists.

The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5-enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg Kg-1 i.p.) or Mr-2266 (2.0 mg kg-1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.

Animals↗
PubMed1982

Some observations on the effects of enantiomers of two benzomorphan narcotic antagonists and atropine on analgesia, tremor and hypothermia produced by oxotremorine.

The action of the benzomorphan narcotic antagonists Mr-1452 and Mr-2266 and their respective (+) isomers Mr-1453 and Mr-2267 as well as the antimuscarinic agent atropine upon oxotremorine (OTMN)-induced analgesia, tremor, and hypothermia were investigated in mice. The (+) isomers Mr-1453 (1.0 mg kg-1 i.p.) and Mr-2267 (2.0 mg kg-1 i.p.), but not the (-) isomers (Mr-1452 and Mr-2266) in doses up to 2.0 mg kg-1 i.p. after 30 min pretreatment produced a significant and parallel shift in OTMN's analgesic dose-response line, assessed by the hot plate test (55 degrees C). None of the isomers tested produced any significant change in OTMN induced tremor or hypothermia. This contrasted with atropine (0.5 mg kg-1 i.p.) which antagonized all three pharmacological parameters. The present data indicate that OTMN-induced analgesia in mice may involve a neuronal substrate which, at least partly, differs from those subserving tremor and hypothermia. In addition it supports the notion that cholinergic analgesia exhibits stereospecific sensitivity to the (+) isomers of narcotic antagonists.

Animals↗