Isolated Guinea Pig Ileum Preparation Research Articles

EVALUATION OF ANTI-ASTHMATIC ACTIVITY OF ETHANOLIC EXTRACT OF CYNODON DACTYLON LEAVES

In the present study Cynodon dactylon leaves ethanolic extract and its chloroform and ethyl acetate fractions were used to evaluate the anti-asthmatic activity, using various experimental in vivo and in vitro animal models. Ethanolic extract of Cynodon dactylon and its chloroform and ethyl acetate fractions were evaluated for its anti-asthmatic activity by in vitro models (isolated guinea pig ileum preparation and isolated guinea pig tracheal chain preparation) in vivo models (Histamine and acetylcholine induced bronchospasm in guinea pigs and milk induced eosinophilia in mice model). Ethanolic extract of Cynodon dactylon and its ethyl acetate fraction at the concentration of 10 mg significantly antagonized the effect of histamine induced contraction on isolated guinea pig ileum preparation. Ethyl acetate fraction of Cynodon dactylon showed the maximum spasmolytic activity and significantly extended the latent period of convulsion as compared to standard (Ketotifen fumarate) upon histamine and acetylcholine exposure in a dose dependent manner. The study concluded that, chloroform and ethyl acetate fractions of Cynadon dactylon was shown significant anti-asthmatic activity.

Bergapten modulates ovalbumin-induced asthma

Prior studies on the anti-inflammatory compound bergapten have shown promise in averting allergic airway hyperresponsiveness. This study sought to establish its possible role in modulating an immunologically-induced airway inflammation and hyperresponsiveness in an ovalbumin model of asthma. Asthma is characterised by inflammation and constriction of the airway passages. Therapy is aimed at bronchodilation and reducing inflammation. Histamine is an inflammatory mediator and involved in immune reactions. It is released from mast cells which are important sentinel cells of the innate immune system involved in the inflammatory response. In the asthma model, ovalbumin solution (2 mg ovalbumin) was administered i.p. as a sensitisation dose on day 1 and on day 14 as a booster dose to sensitise the immune system. This was followed by a 10-day challenge on days 21 – 30 using aerosolised ovalbumin (1% w/v dissolved in phosphate-buffered saline, PBS) at a cut-off latency of 10 min. Bergapten was administered at doses of 3 - 30 mg kg−1 p.o. 1 h prior to each challenge. Times to pre-convulsive dyspnoea were recorded. Guinea-pigs were sacrificed and lungs harvested for histological and antioxidant studies. In determining the effect of bergapten on histamine, an isolated guinea pig ileum preparation by the administration of bergapten (1 – 10 µg ml−1) in the presence of histamine. Bergapten increased times to pre-convulsive dyspnoea in the ovalbumin challenge and reduced pathological damage to bronchial tissue. The deposition of collagen around bronchioles was minimised. Antioxidant studies showed higher catalase and superoxide dismutase activity in groups treated with bergapten. Bergapten produced a rightward shift on the Schild plot analysis with a slope of 1.4 and a pA2 value of 9.3 was obtained in the isolated tissue experiment which confirms that bergapten acts as an antagonist on histaminic H1 receptors. Bergapten modulates inflammation in ovalbumin-induced asthma and antagonises histamine at the H1 receptor.

Anti-allergy and anti-tussive activity of Clitoria ternatea L. in experimental animals

Ethnopharmacological relevanceClitoria ternatea flower is traditionally used in the treatment of respiratory disorders including bronchitis and is one of the ingredients in different Ayurvedic preparations that are used in respiratory disorders. However, till date there is no scientific report on the anti-asthmatic activity of this flower. Aim of the studyEthanolic extract of Clitoria ternatea flowers (ECT) was evaluated for its anti-allergy and anti-tussive potential in experimental animals. Additionally, the anti-inflammatory potential of ECT was carried out to draw a plausible mechanism of action of the drug. Materials and MethodsIn-vitro anti-asthmatic activity of ECT was evaluated in goat tracheal chain and isolated guinea pig ileum preparations. Acute and chronic anti-asthmatic activity of ECT (100, 200 and 400 mg/kg; p.o.) was estimated in histamine aerosol exposed guinea pigs and in OVA sensitized and challenged mice respectively. Anti-tussive activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against sulfur dioxide- and citric acid-induced cough in experimental animals. Moreover, the anti-inflammatory activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against carrageenan- and acetic acid-induced inflammation in rats. ResultsECT attenuated histamine-induced contraction in both goat tracheal chain and isolated guinea pig ileum preparations. ECT (400 mg/kg) attenuated histamine-induced dyspnoea and OVA-induced changes in differential cell count in broncheoalveolar fluid, levels of interleukins (IL-1beta and IL-6) and immunoglobulin (OVA-sensitive IgG1) in animals. ECT (400 mg/kg) further ameliorated sulfur dioxide- and citric acid-induced cough in experimental animals. Additionally, ECT (400 mg/kg) attenuated inflammation in carrageenan and acetic acid challenged rodents. ConclusionsStandardized ECT could be considered as a potential therapeutic alternative in the management of allergy-induced asthma.

Investigation into the mechanism of action of essential oil of Pistacia integerrima for its antiasthmatic activity

Ethnopharmacological relevancePistacia integerrima J.L. Stewart ex Brandis locally known as Karkatashringi is an important medicinal plant whose galls are valued in traditional medicine used in India for the treatment of asthma, chronic bronchitis, phthisis, diarrhea, fever, other ailments for the respiratory tract, and as antispasmodic, carminative, antiamoebic and anthelmintic. However, in vitro and in vivo investigations providing new insights into its pharmacological properties have not been thoroughly investigated yet. The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). MethodsEOPI was tested using in vitro studies such as antioxidant activity, mast cell degranulation, angiogenesis, isolated guinea pig ileum preparation and soyabean lipoxidase enzyme activity. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. ResultsEOPI (5–30µg/ml) inhibits 5-lipoxidase enzyme activity with IC50 of 19.71µg/ml and DPPH scavenging activity up to 100µg/ml with maximum inhibition of 44.93±2.53% at 100µg/ml. Pre-treatment with EOPI inhibited erythropoietin-induced angiogenesis. It showed dose dependent (10, 30 and 100µg/ml) anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation to an extent 19.08±0.47%. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggests that the L-subtype Cav channel is involved in spasmolytic action of EOPI.Treatment with EOPI dose dependently (7.5, 15 and 30mg/kg i.p.) inhibited lipopolysaccharide-induced increase in total cell count, neutrophil count, nitrate–nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Roflumilast was used as a standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. ConclusionThe study demonstrates the effectiveness of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Effect of thienorphine on intestinal transit and isolated guinea-pig ileum contraction

To evaluate the effect of thienorphine on small intestinal transit in vivo and on guinea-pig ileum (GPI) contraction in vitro. The effects of thienorphine on intestinal transit were examined in mice and in isolated GPI. Buprenorphine and morphine served as controls. The distance traveled by the head of the charchol and the total length of the intestine were measured in vivo. Gastrointestinal transit was expressed as a percentage of the distance traveled by the head of the marker relative to the total length of the small intestine. The isolated GPI preparations were connected to an isotonic force transducer and equilibrated for at least 1 h before exposure to drugs. Acetylcholine was used for muscle stimulation. Thienorphine (0.005-1.0 mg/kg, ig) or buprenorphine (0.005-1.0 mg/kg, sc) dose-dependently significantly inhibited gut transit compared with saline. Thienorphine inhibited gut transit less than buprenorphine. The maximum inhibition by thienorphine on the intestinal transit was 50%-60%, whereas the maximum inhibition by morphine on gut transit was about 100%. Thienorphine also exhibited less inhibition on acetylcholine-induced contraction of GPI, with a maximum inhibition of 65%, compared with 93% inhibition by buprenorphine and 100% inhibition by morphine. Thienorphine induced a concentration-dependent decrease in the basal tonus of spontaneous movement of the GPI, the effect of which was weaker than that with buprenorphine. The duration of the effect of thienorphine on the GPI was longer than that with buprenorphine. Thienorphine had less influence, but a longer duration of action on GPI contraction and moderately inhibited intestinal transit.

Synthesis and biological evaluation of N 1,N 2-bis-[4-(t-amino)-2-butynyl]phthalamides as oxotremorine and acetylcholine antagonists

A series of N1,N2-bis-[4-(t-amino)-2-butynyl]phthalamides have been synthesized and investigated for the blocking of the motor effect of oxotremorine in intact mice and for their antagonistic activity towards acetylcholine on isolated guinea pig ileum preparations. All N1,N2-bis-[4-(t-amino)-2-butynyl]phthalamides showed more selectivity as oxotremorine antagonists than atropine and less potent than atropine on peripheral cholinergic antagonistic activity.

Gastroprotective Effect and Safety Assessment of <i>Zanthoxylum Zanthoxyloides</i> (Lam) Waterm Root Bark Extract

Problem statement: Gastrointestinal ulcers account significantly for morbidity and mortality in Ghana. The study therefore investigate d the gastroprotective effect of an ethanolic root bark extract of Zanthoxylum zanthxyloides and its safety for us. Approach: Gastric ulceration was induced in Sprague-Dawley rats with Indomethacin (25 mg kg -1 , p.o) and was treated with 150, 250, or 500 mg kg -1 of the extract, or 20 mg kg -1 Esomeprazole. The number of ulcers per stomach, Ulcerative Index and Curative Ratio were determined. A histolo gical study of the gastric mucosa was also performed. The extract's effect on an isolated guin ea-pig ileum preparation was investigated to elucidate its possible mechanism of action. Safety assessments involving, organ weight to body weight ratio determination, hematological analysis and liv er function tests were performed. Results: The extract significantly decreased (p ≤0.001) the number of ulcers per stomach and the Ulc erative Index (similar to Esomeprazole) and significantly increas ed (p ≤0.001) the Curative Ratio in a dose-dependent manner. It completely corrected the architectural d istortions caused by gastric ulceration and inhibit ed significantly (p ≤0.001) the contractile responses of the isolated gu inea-pig ileum to Acetylcholine, Nicotine and Histamine in a manner comparable to reference antagonists. The extract had no significant effect (p>0.05) on organ weight to body ratio and hematological profile. Plasma levels of Alanine transaminase and Alkaline phosphatase decreased significantly (p ≤0.001) in extract and Esomeprazole-treated ulcerated rats. Levels of Gamma-glutamyl transferase , Total bilirubin (direct and indirect) however increased significantly (p≤0.01-0.001). Conclusion/Recommendations: Per the findings, the ethanolic root bark extract of Zanthoxylum zanthoxyloides has gastroprotective effect in Sprague-Dawley rats working possibly via antimuscarinic or antihistaminic mechanism. It however has a potential of causing cholestasis hence liver func tion should be monitored.

General Pharmacology Studies on ß-Domain Deleted Recombinant Factor VIII

beta-Domain deleted recombinant factor VIII (GC-rAHF), newly developed by Korea Green Cross Co., is a novel therapeutic for hemophiliacs and is currently under clinical evaluation. The general pharmacological properties of this drug were evaluated using mice, rats, guinea pigs and rabbits. Intravenous doses of 5 to 500 IU/kg were assayed in several tests to analyze their effects in vivo on various systems. The effect of the substance under study was also tested in vitro on isolated guinea pig ileum preparations at final concentrations of 5 to 50 IU/kg. The result of this study showed that GC-rAHF did not affect general behavior in the Irwin test. Similarly the drug was not found to affect neither normal body temperature nor the spontaneous activity in mice. In addition, it was not found to induce pharmacologically significant alterations of the cardiovascular and respiratory parameters in rats. No effects were observed either in the pentobarbital sodium-induced sleep-induction time and duration, in writhing test or in the test of pentetrazole-induced convulsion. Finally, the tested drug did not modify the gastrointestinal motility, acetylcholine or histamine-induced contraction of the isolated guinea pig ileum, nor gastric secretion. The results demonstrated that GC-rAHF has no effects on the central nervous, cardiovascular, respiratory and digestive systems in the doses of 5, 50 and 500 IU/kg in vivo and 5, 10, 50 and 100 IU/kg in vitro.

Maximal responses in guinea-pig isolated ileum preparations: influence of longitudinal and circular muscle.

Maximal responses in guinea-pig isolated ileum preparations: influence of longitudinal and circular muscle.

Effects of two cholinesterase inhibitors on acetylcholine release from the guinea-pig isolated ileum preparation.

Journal Article Effects of two cholinesterase inhibitors on acetylcholine release from the guinea-pig isolated ileum preparation Get access B Cox, B Cox Department of Pharmacology, University of Manchester, Manchester, M13 9PL, UK Search for other works by this author on: Oxford Academic Google Scholar Sally E Hecker, Sally E Hecker Department of Pharmacology, University of Manchester, Manchester, M13 9PL, UK Search for other works by this author on: Oxford Academic Google Scholar A H Weston A H Weston Department of Pharmacology, University of Manchester, Manchester, M13 9PL, UK Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 22, Issue 3, March 1970, Pages 231–232, https://doi.org/10.1111/j.2042-7158.1970.tb08505.x Published: 12 April 2011 Article history Received: 17 December 1969 Published: 12 April 2011

Use of the mouse jumping test for estimating antagonistic potencies of morphine antagonists.

The potencies of 19 reference morphine antagonists have been compared in a modified version of the mouse jumping test. Mice were each implanted subcutaneously with one 75 mg pellet of morphine. Antagonist challenge took place 72 h later and the incidence of repetitive vertical-jumping was monitored over 1 h. A high Pearson correlation coefficient (r = 0.997) was found between quantitative assays based on the total number of jumps per mouse and quantal assays based on mice jumping at least 6 times. A comparison of relative potencies obtained with the mouse test and with non-withdrawn morphine-dependent monkeys gave a Spearman rank order coefficient of 0.91 while a similar comparison with values obtained with the guinea-pig isolated ileum preparation also gave a high correlation coefficient (r= 0.92). Whereas it is difficult to assess the antagonistic component of buprenorphine and cyclorphan with the ileum preparation, both compounds can be satisfactorily assayed in the mouse jumping test. The reported antagonistic properties of ketocyclazocine and profadol could not be confirmed in the mouse model.

An investigation of the effects of angiotensin on the release of neurohumoral transmitters at motor, adrenergic and cholinergic nerve terminals.

Abstract On the sciatic nerve-gastrocnemius-soleus muscle preparation of the cat, angiotensin (1–5 μg/kg, i.v.) potentiated the twitch response to maximal and submaximal stimulation of the sciatic nerve and produced partial reversal of an incomplete tubocurarine blockade. These actions could not be explained in terms of increased acetylcholine release since they were not seen in isolated motor nerve-striated muscle preparations and were probably secondary to the cardiovascular actions of angiotensin. Blockade of conduction in the postganglionic cholinergic nerves in the guinea-pig isolated ileum preparation by cooling or anoxia antagonized the response of this tissue to angiotensin. These procedures left the response to exogenous acetylcholine unchanged though they removed the cholinergic component of the response to angiotensin which is known to be present in this tissue. No evidence of increase in catecholamine output could be found in preparations of guinea-pig and rabbit vasa deferentia or rabbit duodenum responding to submaximal stimulation of their adrenergic nerves. It is concluded that angiotensin has no direct action on the stores of neurohumoral transmitter at motor, postganglionic cholinergic or postganglionic adrenergic nerves and that its known acetylcholine releasing action in the isolated ileum results from stimulation of the ganglia.

Can the effects of meptazinol on the guinea-pig isolated ileum be explained by inhibition of acetylcholinesterase?

It has previously been shown that there is a cholinergic component in the antinociceptive action of the opioid analgesic drug meptazinol. In the present study meptazinol was shown to be an inhibitor of acetylcholinesterase in-vitro with a potency one hundredth that of physostigmine. This activity was found to reside only in the (-)-enantiomer of meptazinol. The anticholinesterase activity of meptazinol may explain the increase in the size of the electrically-evoked contraction of the guinea-pig isolated ileum preparation since by using a long pulse width (5 ms) it was found that the (-)-enantiomer of meptazinol modified only the component of the response due to neuronally released acetylcholine and had no direct effect on the smooth muscle. This property of meptazinol may also be responsible for the cholinergic effects of the drug in-vivo.

Studies on Anti-Asthmatic Property of Cyamopsis tetragonoloba (L.) Taub. Leaf Extracts

Objectives: The present study has been designed to evaluate the anti-asthmatic activity of leaves of Cyamopsis tetragonoloba on in-vitro and in-vivo models. Material and methods: The anti-asthmatic activity was carried out on isolated guinea pig ileum preparation (in-vitro), histamine induced bronchospasm in guinea pigs and milk-induced leukocytosis and eosinophilia in mice. Results: Results showed that, the aqueous extract of the leaves significantly inhibited (p<0.05) the contractile effect of histamine. Both Aqueous and alcoholic extracts were found to inhibit (p<0.001 and p<0.05) bronchospasm induced by histamine in guinea pigs by varying degree. Treatment with aqueous as well as alcoholic extracts of the plant decrease blood eosinophilia and leukocyte count by 80% and 90% respectively. Conclusion: The leaves of the plant showed significant anti-histaminic effect in both in-vitro and in-vivo models and adaptogenic activity, thus can be consider being use full in treatment of asthma.

Evaluation of antiasthmatic activity ofCurculigo orchioidesgaertn. rhizomes

The ethanol extract of Curculigo orchioides was evaluated for antiasthmatic activity by using various in vitro and in vivo animal models. In vitro models like isolated goat tracheal chain preparation and isolated guinea pig ileum preparation were studied to know basic mechanism by which extract shows relaxant activity. The study showed that extract is effective against histamine-induced contraction. In isolated goat tracheal chain preparation and isolated guinea pig ileum preparation extract exhibits maximum relaxant effect (p< 0.01) against histamine at concentrations 100μg/ml and 25μg/ml respectively. Animal studies involved use of histamine induced bronchoconstriction in guinea pigs, egg albumin induced passive paw anaphylaxis in rats and haloperidol-induced catalepsy in mice. These studies showed significant (p< 0.01) protection at lower doses while further increase in the dose level showed reduced activity. Biochemical estimations in milk-induced total leukocytes count and milk-induced differential leukocyte count were also studied. In this study there was maximum increase in leucocytes and lymphocytes (99%) and maximum decrease in eosinophils up to 0% at dose 375mg/kg p.o. body weight was observed. The results of these studies indicated usefulness of ethanol extract of Curculigo orchioides in asthma.

5-HT3 Serotonin Receptor Agonists: A Pharmacophoric Journey

It has been nearly 50 years since Gaddum and Picarelli characterized serotonin M-receptors using an isolated guinea pig ileum preparation; M-receptors, known today as 5-HT3 receptors, are just one of about fifteen different types of serotonin receptors. The discovery of this new class of serotonin receptors evoked a necessity for new ligands to study their pharmacological activity. Today, several 5-HT3 ligands are employed therapeutically in the treatment of emesis, with further potential for the treatment of migraine and numerous central nervous disorders. Using radioligand binding techniques several chemical classes of compounds have been identified and investigated. These studies led to formulation of structure-affinity relationships (SAFIR) and the first two-dimensional pharmacophore model for 5-HT3 receptor ligand binding. Since then, several new SAFIR studies have been conducted and new, more advanced three-dimensional pharmacophore models have been proposed using molecular modeling techniques. In diverse functional assays, the majority of reported 5-HT3 derivatives that meet the established pharmacophore model requirements showed antagonist activity. Structure-activity relationships (SAR) for various classes of 5-HT3 receptor antagonists have been developed. The introduction of m-chlorophenylbiguanide (m-CPBG), a reasonably selective 5-HT3 agonist, called for redefinition of existing pharmacophores. In general, 5-HT3 agonists failed to adhere to 5-HT3 pharmacophore models. This triggered new studies leading to formulation of SAFIR and SAR for agents with 5-HT3 receptor agonist activity. Progress in the development of 5-HT3 agonists and proposed agonist pharmacophore models are reviewed.

Anti-diarrheal and spasmolytic activities and acute toxicity study of Soonkijangquebo, a herbal anti-diarrheal formula

The anti-diarrheal and spasmolytic activities of Soonkijangquebo™ (SKJQB), a Korean herbal anti-diarrheal formulation, were subjected to pharmacological evaluation. SKJQB, at a dose of 50–200 mg/kg, inhibited castor oil-induced diarrhea in mice. The median effective dose (ED 50) for the anti-diarrheal effect was 93 mg/kg. In isolated rabbit jejunum preparations, SKJQB produced a spasmolytic effect by the relaxation of spontaneous contractions in a dose-dependent manner. The median effective concentration (EC 50) for the spasmolytic effect was 3.6 mg/ml. In isolated guinea pig ileum preparations, SKJQB also produced a spasmolytic effect by reduction of acetylcholine-induced contractions. When tested against calcium channel blockade in rabbit jejunum, SKJQB caused a dose-dependent rightward shift in the Ca 2+ dose–response curves, similar to that produced by verapamil, a well-known calcium antagonist. In an acute toxicity study in Sprague–Dawley rats, the median lethal dose (LD 50) of SKJQB was greater than 2000 mg/kg, and no pathological changes were noticed in macroscopic examination by necropsy of rats treated with SKJQB. Thus, SKJQB may be safely used as a spasmolytic as well as an anti-diarrheal agent.

Synthesis and Evaluation of Novel 2-Oxo-1,2-dihydro-3-quinolinecarboxamide Derivatives as Potent and Selective Serotonin 5-HT4 Receptor Agonists.

A series of 8'-substituted N-(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized. The 5-HT4 receptor agonistic activity was evaluated using the isolated guinea pig ileum preparation. Of the compounds synthesized, N-(endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (15a, TS-951) exhibited the most potent serotonin 5-HT4 receptor agonistic activity. This compound had a high affinity for the serotonin 5-HT4 receptor although it had no affinities for other broad spectrum receptors. Furthermore, it remarkably enhanced gastrointestinal motility in conscious fed dogs without unfavorable effects that non-selective serotonin 5-HT4 receptor agonist has. TS-951 may be useful in improving gastrointestinal dysfunction.

Selective potentiation by ouabain of naloxone‐induced withdrawal contractions of isolated guinea‐pig ileum following acute exposure to morphine

1. Ouabain, an inhibitor of Na+/K+ ATPase induces the release of acetylcholine from central and myenteric cholinergic neurones principally due to partial depolarization of the cell membrane. The effect of ouabain has been examined on neurogenic contractions in the guinea-pig ileum arising from either electrical field stimulation or from naloxone in morphine-exposed preparations. 2. Guinea-pig isolated ileum preparations were stimulated transmurally (0.1 Hz, 0.3 ms, 200 mA) to elicit contractions of the myenteric plexus-longitudinal smooth muscle. 3. Incubation with morphine (0.3 microM, 60 min) was followed by naloxone (1 microM) which produced withdrawal contractions in 16/26 preparations (median of 10.7 [2.2-40.0]% of a maximal contracture to KCl (60 mM)). 4. In parallel experiments, ouabain (1 microM) was added to the tissue before exposure to morphine (0.3 microM, 60 min). Naloxone (1 microM) subsequently displayed a withdrawal contraction in all 26/26 tissues (57.9 [30.5-151.7]% of a maximal contracture to KCl (60 mM). 5. Ouabain neither affected the concentration-dependent contractions of guinea-pig ileum produced by carbachol nor the inhibition of electrically-evoked contraction produced by morphine (0.3 microM). 6. The muscarinic antagonist atropine (0.1 microM) antagonized control naloxone withdrawal responses. The atropine resistant component, evident in ouabain-treated tissues, was blocked by SR140333((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenyla cetyl)piperidin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2. 2]-octane, chloride), a substance P antagonist. 7. Clonidine (alpha2-adrenoceptor agonist) inhibited electrically-evoked contractions. Exposure to the alpha2-adrenoceptor antagonist RX811059 (2-(2-ethoxy-1,4-benzodioxan-2-yl)-2-imidazoline), resulted in a contracture which was not significantly enhanced by ouabain (1 microM). 8. Ouabain selectively potentiates the naloxone-induced withdrawal contraction following acute exposure to morphine the major components of which are mediated by both acetylcholine and substance P.

The Pharmacology of Physostigmine

The Pharmacology of Physostigmine