The properties of the clonidine withdrawal response of guinea‐pig isolated ileum

Chahl, Loris A.

doi:10.1111/j.1476-5381.1985.tb08882.x

Cited by 18 publications

(15 citation statements)

References 20 publications

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“…The washout contracture to adenosine, 5,uM, was abolished in seven preparations (from seven animals) by addition of the SP antagonist, spantide, 1O#UM, 30s before washout of the bath (Figure 1). Thus adenosine produced similar actions on the ileum to those previously described for MEnk and noradrenaline (Chahl, 1983;1985). The lack of response to washout of somatostatin, 5 M, is shown in Figure 2.…”

Section: Effects Of Washoutsupporting

confidence: 73%

“…Lack of effect of ocreotide on naloxone-precipitated MEnk withdrawal is shown in Figure 4. In three preparations somatostatin at a concentration of 5OpuM, did not inhibit the naloxone-precipitated MEnk withdrawal response, but in another three preparations, baclofen, (Chahl, 1986), and phentolamine precipitated withdrawal following 2 min contact with clonidine (Chahl, 1985). In the present experiments concentrations of naloxone (1pM) which precipitated withdrawal from pureceptor agonists (Chahl, 1986), did not produce a withdrawal contracture from the K-agonist, U-50,488H.…”

Section: Effects Of Agonists On the Opioid Withdrawal Responsecontrasting

confidence: 47%

“…[Met5]enkephalin (Chahl, 1985) Noradrenaline (Chahl, 1985 (8) nil (9) (5 pM) contraction (5pM) 32 + 4 (15) nil (6) (5pM) nil (5) ( 5pM) nil (3) nil (3) nil (2) nil (7) (5puM)…”

Section: Effects Of Agonists On Guinea-pig Ileummentioning

confidence: 99%

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Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met⁵] enkephalin

Chahl

1990

British J Pharmacology

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1 Brief exposure for 2 min of guinea-pig isolated ileum to [Met5]enkephalin (MEnk) and noradrenaline has been shown previously to produce withdrawal contractures on washout of the agonist or addition of naloxone (MEnk) or phentolamine (noradrenaline). 2 The present study was undertaken to investigate firstly, whether other putative neurotransmitters and/or related drugs which inhibit transmitter release also produced withdrawal responses following 2 min contact with the ileum and secondly, whether they affected the opioid withdrawal response.3 Adenosine (1-5 uM), but not U-50,488H (1-5 pM), somatostatin (0.01-5 pM), ocreotide (1-5 UM), baclofen(1-25uMm) or dopamine (5, 5O#M), produced a contracture on washout following 2min contact with the ileum. The adenosine (5,UM) washout contracture, in common with MEnk and noradrenaline washout contractures, was inhibited by the substance P antagonist, spantide (10pM).4 Added 30s before washout at a concentration of 5pgM, noradrenaline, U-50,488H, adenosine, somatostatin and ocreotide significantly inhibited the washout withdrawal response following 2 min contact of the ileum with MEnk, 1 M. A higher concentration of baclofen, 250,UM, also inhibited this response. 5 The naloxone (1 pM)-precipitated withdrawal response following contact of the ileum with MEnk, 1 ,UM, for 2 min, was inhibited only by noradrenaline (5pM) and U-50,488H (5pM). 6 It is concluded that during naloxone-precipitated opioid withdrawal an additional population of enteric motor neurones is recruited which is not involved in the washout withdrawal response and these neurones have less diversity of presynaptic receptors mediating inhibition of transmitter release than cholinergic motor neurones.

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Section: Effects Of Washoutsupporting

confidence: 73%

Section: Effects Of Agonists On the Opioid Withdrawal Responsecontrasting

confidence: 47%

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Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met⁵] enkephalin

Chahl

1990

British J Pharmacology

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“…Barrios et al (1993) reported that yohimbine precipitated withdrawal signs, such as jerks, head-shakes, defaecation, and weight loss in clonidinetreated mice. The clonidine withdrawal phenomenon is also demonstrated in isolated organs (Chahl 1985;Barrios et al 1993). These analogies suggest that similar mechanisms exist between the developments of dependence in the a 2 -adrenoceptor and opioid systems (Duggan et al 1994).…”

Section: Discussionmentioning

confidence: 89%

Lithium Inhibits the Development of Physical Dependence to Clonidine in Mice

Dehpour¹,

Sadr

Roohi-Azizi

et al. 2002

Pharmacology & Toxicology

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Based on our previous finding that chronic lithium treatment reduced naloxone-precipitated withdrawal syndrome in morphine-treated mice, the effect of chronic lithium treatment was evaluated on the development of dependence to clonidine. Dependence was induced by injection of either morphine (50, 50 and 75 mg/kg, intraperitoneally with 3 hr interval for 3 consecutive days), or clonidine (2 mg/kg/day, intraperitoneally for 10 days). Naloxone (4 mg/kg, intraperitoneally) precipitated withdrawal signs in both morphine-and clonidine-treated mice. Yohimbine (5 mg/kg, intraperitoneally) precipitated withdrawal signs in the clonidine-treated mice, similar to morphine withdrawal signs; but failed to precipitate any significant sign in the morphine-treated mice. Coadministration of lithium was carried out by adding lithium chloride to drinking water (600 mg/l for 20 days; 10 days before the beginning of clonidine administration and 17 days before the administration of morphine to allow the lithium concentration to reach steady-state). The results indicated that chronic lithium administration significantly attenuated the withdrawal signs, precipitated either by yohimbine or naloxone, in clonidine-treated mice. As a conclusion, clonidine withdrawal signs are very similar to opioid withdrawal signs, and lithium is able to prevent the development of physical dependence to clonidine.

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“…The propulsion can be delayed by clonidine and loperamide, an adrenergic ␣ 2 -receptor ag-onist and an -opioid receptor agonist, respectively [6] . It is well known that clonidine relaxes isolated intestine [7,8] and loperamide causes compulsive contractions in the gastrointestinal tract [9] . However, the clonidine-and loperamide-induced delay in the models of colonic propulsion has not been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Two Models of Drug-Induced Constipation in Mice and Evaluation of Mustard Oil in These Models

et al. 2009

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Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. Both loperamide and clonidine dose-dependently prolonged the evacuation time. Clonidine (10 μg/kg) and loperamide (0.3 mg/kg) tripled the evacuation time compared to controls. These delays were antagonized by the administration of yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor-stimulating drug, reversed the delay in both models, but the effects were diminished at high doses. Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.

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The properties of the clonidine withdrawal response of guinea‐pig isolated ileum

Cited by 18 publications

References 20 publications

Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met⁵] enkephalin

Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met⁵] enkephalin

Lithium Inhibits the Development of Physical Dependence to Clonidine in Mice

Characterization of Two Models of Drug-Induced Constipation in Mice and Evaluation of Mustard Oil in These Models

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The properties of the clonidine withdrawal response of guinea‐pig isolated ileum

Cited by 18 publications

References 20 publications

Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met5] enkephalin

Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met5] enkephalin

Lithium Inhibits the Development of Physical Dependence to Clonidine in Mice

Characterization of Two Models of Drug-Induced Constipation in Mice and Evaluation of Mustard Oil in These Models

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Product

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Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met⁵] enkephalin

Effects of putative neurotransmitters and related drugs on withdrawal contractures of guinea‐pig isolated ileum following brief contact with [Met⁵] enkephalin