Tachykinin antagonists inhibit the morphine withdrawal response in guinea-pigs

Johnston, Paul A.; Chahl, Loris A.

doi:10.1007/bf00251127

Cited by 35 publications

(13 citation statements)

References 30 publications

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“…The reasons for these dierential eects are not known, but could be related to dierential action of CGRP 8-37 on the CGRP and substance P containing neurones in the dorsal horn. Currently, the role of substance P in opioid tolerance is largely unde®ned although previous studies have implicated this peptide in the development of physical dependence (Johnston & Chahl, 1991;Kreeger & Larson, 1993). An increase in the release of substance P could lead to the release of retrograde messengers and the attenuation of opioid receptor activity.…”

Section: Discussionmentioning

confidence: 99%

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Powell

Sutak

et al. 2000

British J Pharmacology

108

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1 This study examined the eects of the peptide CGRP receptor antagonist CGRP and the newly-developed non-peptide CGRP receptor antagonist BIBN4096BS for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. 2 Repeated administration of intrathecal morphine (15 mg), once daily, produced a progressive decline of antinociceptive eect and an increase in the ED 50 value in the tail¯ick and paw pressure tests. Co-administration of CGRP 8-37 (4 mg) or BIBN4096BS (0.05, 0.1 mg) with morphine (15 mg) prevented the decline of antinociceptive eect and increase in ED 50 value in the tail¯ick test. Intrathecal administration of the CGRP receptor antagonists did not alter the baseline responses in either tests. Acute CGRP 8-37 also did not potentiate the acute actions of spinal morphine. 3 In animals rendered tolerant to intrathecal morphine, subsequent administration of CGRP (4 mg) with morphine (15 mg) partially restored the antinociceptive eect and ED 50 value of acute morphine, re¯ecting the reversal of tolerance. 4 Animals tolerant to intrathecal morphine expressed increased CGRP and substance P-like immunostaining in the dorsal horn of the spinal cord. The increase in CGRP, but not substance Plike immunostaining, was blocked by a co-treatment with CGRP 8-37 (4 mg). In animals already tolerant to morphine, the increase in CGRP but not substance P-like immunostaining was partially reversed by CGRP 8-37 (4 mg). 5 These data suggest that activation of spinal CGRP receptors contributes to both the development and expression of spinal opioid tolerance. CGRP receptor antagonists may represent a useful therapeutic approach for preventing as well as reversing opioid tolerance.

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Section: Discussionmentioning

confidence: 99%

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Powell

Sutak

et al. 2000

British J Pharmacology

108

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“…Central injection of SP and selective NK 1 , NK 2 and NK 3 receptor agonists induced increased locomotor activity and other behaviors such as face-washing, grooming and wet-dog shakes [129][130][131][132][133]. The vocalization response induced in guinea-pigs by NK 1 receptor agonists was of particular interest since it was considered to be a stress-induced response [134].…”

Section: Tachykinins In Affective Disordersmentioning

confidence: 98%

“…Peptide SP antagonists [129] and a non-peptide NK 1 receptor antagonist [205] were reported to reduce the signs of opioid withdrawal in animals. The presence of tachykinins in the mesolimbic system suggested that they may also be involved in reward and reinforcing mechanisms which lead to addiction.…”

Section: Tachykinins In Drug Abusementioning

confidence: 99%

Tachykinins and Neuropsychiatric Disorders

Chahl

2006

CDT

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The classical tachykinins, substance P, neurokinin A and neurokinin B are predominantly found in the nervous system where they act as neurotransmitters and neuromodulators. Their respective preferred receptors are NK1, NK2, and NK3 receptors. The presence of substance P in nociceptive primary afferent neurons, electrophysiological studies showing that it activated neurons in the dorsal horn of the spinal cord, and behavioral studies in animals, supported the concept that substance P was an important transmitter in the nociceptive pathway. It was therefore surprising that non-peptide NK1 receptor antagonists were ineffective as analgesics in clinical pain conditions. Nevertheless, the discovery that NK1 receptor antagonists had antidepressant activity led to renewed interest in these antagonists. It is disappointing that clinical trials of MK869 (aprepitant) for depression were suspended. The future of NK1 receptor antagonists as antidepressant drugs will depend on the outcome of clinical trials with other NK1 receptor antagonists. NK1 receptor antagonists were also found to be effective antiemetics, and aprepitant has recently become available for the treatment of chemotherapy induced emesis. Although less is known of the potential of NK2 and NK3 receptor antagonists, recent trials of NK3 receptor antagonists have shown efficacy in schizophrenia. The discovery of a new family of tachykinins, the hemokinins and endokinins, which acts on NK1 receptors and has potent effects on immune cells, has implications for the clinical use of NK1 receptor antagonists. Thus specific therapeutic strategies may be required to enable NK1 receptor antagonists to be introduced for treatment of neuropsychiatric disorders.

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“…washing and lachrymation have been reported (Brent et al, 1988;Elliott et al, 1991;Johnston & Chahl, 1991;Chahl & Johnston, 1993). A controversy exists concerning the existence of NK2 tachykinin receptors in the central nervous system (Quirion & Dam, 1988;Saffroy et al, 1988;Dam et al, 1990;Hagan et al, 1993;Maggi et al, 1993a).…”

Section: Introductionmentioning

confidence: 98%

Comparative behavioural profile of centrally administered tachykinin NK₁, NK₂ and NK₃ receptor agonists in the guinea‐pig

Piot

Betschart

Grall

et al. 1995

British J Pharmacology

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Tachykinin antagonists inhibit the morphine withdrawal response in guinea-pigs

Cited by 35 publications

References 30 publications

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Tachykinins and Neuropsychiatric Disorders

Comparative behavioural profile of centrally administered tachykinin NK₁, NK₂ and NK₃ receptor agonists in the guinea‐pig

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Tachykinin antagonists inhibit the morphine withdrawal response in guinea-pigs

Cited by 35 publications

References 30 publications

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Blockade and reversal of spinal morphine tolerance by peptide and non‐peptide calcitonin gene‐related peptide receptor antagonists

Tachykinins and Neuropsychiatric Disorders

Comparative behavioural profile of centrally administered tachykinin NK1, NK2 and NK3 receptor agonists in the guinea‐pig

Contact Info

Product

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About

Comparative behavioural profile of centrally administered tachykinin NK₁, NK₂ and NK₃ receptor agonists in the guinea‐pig