Chapter 26 Serotonin receptor subtypes and the modulation of pain transmission

Fp, Zemlan; Behbehani, MM; Rm, Murphy

doi:10.1016/s0079-6123(08)62801-0

Cited by 53 publications

(21 citation statements)

References 26 publications

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“…In agreement with the inferences from the in vitro studies, anpirtoline also behaved as a 5-HTIB receptor agonist in these two tests since it reversed the isolation-induced social behaviour deficit in mice, as did the 5-HT1B receptor agonist TFMPP (Titeler et al, 1987;Schechter, 1988; see Table 4), and increased the nociceptive threshold in the electrostimulated pain-test, as previously found with the potent 5-HTIB receptor agonists, TFMPP and m-chlorophenyl-piperazine (Zemlan et al, 1988). In addition to 5-HT1B receptor agonists, opiates and x2-adrenoceptor agonists also exhibit antinociceptive properties in relevant animal tests (Sullivan et al, 1987;Yaksh & Stevens, 1988 Another interesting property of anpirtoline is its antidepressant-like action in the forced swimming test (Porsolt et al, 1977) in rats.…”

Section: Discussionsupporting

confidence: 88%

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Schlicker

Ulrich²,

Hamon

et al. 1992

British J Pharmacology

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3 Like 5-HT, anpirtoline concentration-dependently inhibited forskolin-stimulated adenylate cyclase activity in homogenates from the rat substantia nigra. Both effects were not additive, and could be prevented by 5-HTlB receptor antagonists such as propranolol and penbutolol.4 In superfused rat and pig brain cortex slices preincubated with [3H]-5-HT, the electrically evoked tritium overflow was inhibited by anpirtoline and 5-HT. Whereas 5-HT was equipotent in both tissues (EC50 = 69 nM), anpirtoline was markedly less potent in pig brain cortex slices (EC50 = 1190 nM) than in rat brain cortex slices (EC50 = 55 nM). The concentration-response curve for anpirtoline was shifted to the right by metitepine in both preparations. 5 In the social behaviour deficit test, anpirtoline and trifluoromethylphenyl-piperazine were effective in reversing the isolation-induced impairments in mice, an effect shown only by compounds with agonist properties at the 5-HTIB receptor.6 In the electrostimulated pain test using mice, anpirtoline dose-dependently increased the pain threshold with an ED50 of 0.52mgkg-1, i.p. The antinociceptive activity of anpirtoline was abolished by pretreatment with cyproheptadine or propranolol. 7 In the forced swimming test in rats, anpirtoline induced a dose-related increase in swimming activity. With an ED50 value of 4.6mgkg-1, i.p., anpirtoline was 4 times more potent than the two standard compounds imipramine and desipramine. The decrease of immobility time or the increase of active periods in this model of behavioural despair is suggested to be characteristic of ant-depressant drugs. 8 Anpirtoline exhibits both antinociceptive and antidepressant-like activities in animals. It is probable that anpirtoline elicits these pharmacological effects via its agonist effect on 5-HT1B and 5-HT1A receptors.

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Section: Discussionsupporting

confidence: 88%

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Schlicker

Ulrich²,

Hamon

et al. 1992

British J Pharmacology

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“…There is much debate on the roles of 5-HT receptors in general, and 5-HTIA-receptors in particular, in controlling transmission through the spinal cord. Most of the evidence supporting a role for 5-HT in tonic descending inhibition is based on the effects of the non-selective 5-HTI/2-receptor antagonist/partial agonist drug methysergide (Engberg et al, 1968;Rivot et al, 1987; see Duggan & Morton, 1988 (Nagano et al, 1988;Zemlan et al, 1988;Bras et al, 1990;Jackson & White, 1990;Wang & Dun, 1990;Crick & Wallis, 1991;Bervoets et al, 1993;Alhaider & Wilcox, 1993;Ali et al, 1994;Clarke et al, 1994;Hasegawa & Ono, 1996; see also Cesselin et al, 1994;Millan, 1995). Inhibitory effects of 5-HTIA-receptor agonists have been most commonly observed on responses evoked by stimulation of low-threshold afferent fibres.…”

Section: -Htia-receptors and Tonic Descending Inhibitionmentioning

confidence: 99%

Spinal 5‐HT‐receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit

Clarke

Harris

Houghton

1996

British J Pharmacology

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1 In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HTlAreceptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sural nerve. The approximate ED50 for WAY-100635 was 0.9 nmol and that for (S)WAY-100135 13 nmol. Intrathecal doses of the antagonists which caused maximal facilitation of reflexes in non-spinalized rabbits had no effect in spinalized preparations. 2 In non-spinalized animals, intravenous administration of (S)WAY-100135 was significantly less effective in enhancing reflexes than when it was given by the intrathecal route.3 When given intrathecally, the selective 5-HT2A/2c-receptor antagonist, ICI 170,809, produced a bellshaped dose-effect curve, augmenting reflexes at low doses (,<44 nmol), but reducing them at higher doses (982 nmol). Idazoxan, the selective 22-adrenoceptor antagonist, was less effective in enhancing reflex responses when given intrathecally after ICI 170,809 compared to when it was given alone. Intravenous ICI 170,809 resulted only in enhancement of reflexes and the facilitatory effects of subsequent intrathecal administration of idazoxan were not compromised. 4 The selective 5-HT3-receptor blocker ondansetron faciliated gastrocnemius medialis reflex responses in a dose-related manner when given by either intrathecal or intravenous routes. This drug was slightly more potent when given i.v. and it did not alter the efficacy of subsequent intrathecal administration of idazoxan. 5 None of the antagonists had any consistent effects on arterial blood pressure or heart rate. 6 These data are consistent with the idea that, in the decerebrated rabbit, 5-HT released from descending axons has multiple roles in controlling transmission through the sural-gastrocnemius medialis reflex pathway. Thus, it appears 5-HT tonically inhibits transmission between sural nerve afferents and gastrocnemius motoneurones by an action at spinal 5-HTlA-receptors. Spinal 5-HT2A/2C-receptors may mediate a weak inhibition of transmission in the spinal cord, but more convincing evidence was obtained for their involvement in descending facilitatory tone. Further, some of the facilitatory consequences of spinal a2-adrenoceptor blockade may be mediated through 5-HT2 type receptors. Spinal 5-HT3 receptors do not appear to have a major role in tonic modulation of the sural-gastrocnemius medialis reflex.

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“…Thus, anpirtoline appears to possess a strong analgesic action which may be mediated via 5-HTI receptors in the central nervous system [5][6][7][8]. To investigate its potential analgesic action in man we have used a technique involving measurement of chemo-somatosensory event-related potentials (CSSERP) after painful stimulation of the nasal mucosa with carbon dioxide [9].…”

Section: Introductionmentioning

confidence: 99%

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

Hummel

Friedel

et al. 1994

Brit J Clinical Pharma

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1 The pain relieving properties of imipramine (100 mg orally), tramadol (150 mg orally), and anpirtoline (60 mg orally) were compared in 16 healthy subjects in a cross-over, double-blind, randomized, and placebo-controlled study. Anpirtoline exhibits analgesia which is possibly mediated via serotoninergic pathways, whereas tramadol exerts its effects at opioid receptors. The pain-relieving effect of the tricyclic antidepressant imipramine may involve both serotoninergic and opioid mechanisms. 2 Chemo-somatosensory event-related potentials (CSSERP) were recorded after painful stimulation of the nasal mucosa with carbon dioxide. Subjects rated the perceived intensity of the stimuli by means of a visual analogue scale. In addition, acoustically evoked responses were recorded, the spontaneous EEG was analyzed in the frequency domain, the subjects' vigilance was assessed in a tracking task, and side effects of the drugs were monitored. 3 Anpirtoline and tramadol produced a decrease of both CSSERP amplitudes and subjective estimates of pain, the effects of the former compound being greater. In contrast, after administration of imipramine no change of CSSERP amplitudes could be detected, whereas the subjective estimate of pain intensity decreased significantly. This was accompanied by a significant decrease of arousal indicating that pain relief produced by acute administration of imipramine was primarily related to its sedation action.4 The analgesic properties of anpirtoline were demonstrated in man. Tramadol was characterized as a weak opioid analgesic. In contrast, imipramine appeared to produce its pain-relieving effects predominantly by non-specific actions. It is hypothesized that different analgesics may change ERP sources in a drug-specific manner.

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Chapter 26 Serotonin receptor subtypes and the modulation of pain transmission

Cited by 53 publications

References 26 publications

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Spinal 5‐HT‐receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

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Chapter 26 Serotonin receptor subtypes and the modulation of pain transmission

Cited by 53 publications

References 26 publications

Anpirtoline, a novel, highly potent 5‐HT1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Anpirtoline, a novel, highly potent 5‐HT1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Spinal 5‐HT‐receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

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Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents