The antinociceptive effect of trazodone in mice is mediated through both μ-opioid and serotonergic mechanisms

Schreiber, Shaul; Backer, Maria M; Herman, I.; Shamir, D.; Boniel, Tal; Pick, Chaim G.

doi:10.1016/s0166-4328(00)00185-6

Cited by 41 publications

(27 citation statements)

References 23 publications

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“…or i.c.v. The few works that have studied the influence of specific opioid receptor antagonists on the antinociceptive effect of ADs have exclusively used systemic administration of these ligands (Gray et al, 1998;Schreiber et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…ADs are able to displace radiolabeled opioid receptor ligands from their binding sites and, after repeated administration, to modify the density of opioid receptors (Isenberg and Cicero, 1984;Hamon et al, 1987). Several studies have evidenced the inhibition of the antinociceptive effect of ADs by naloxone (Ardid and Guilbaud, 1992;Valverde et al, 1994;Gray et al, 1998;Schreiber et al, 2000), an opioid receptor antagonist, and its enhancement by enkephalinase inhibitor (Gray et al, 1998). However, few studies have been conducted to determine the involvement of the different opioid receptor subtypes in the analgesic effect of ADs.…”

mentioning

confidence: 99%

“…However, few studies have been conducted to determine the involvement of the different opioid receptor subtypes in the analgesic effect of ADs. Schreiber et al (2000) and Gray et al (1998) demonstrated that the antinociceptive effect of different ADs was mainly influenced by different opioid receptor antagonists. However, these studies failed to determine the involvement of a specific opioid subtype receptor according to the ADs used.…”

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confidence: 99%

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Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Marchand

Ardid²,

Chapuy³

et al. 2003

J Pharmacol Exp Ther

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The mechanisms of involvement of the opioidergic system in the antinociceptive effect of antidepressants remain to be elucidated. The present study was designed to determine what type of opioid receptors may be involved at the spinal and supraspinal levels in the antihyperalgesic effect of clomipramine, a tricyclic antidepressant commonly prescribed in the treatment of neuropathic pain. Its antihyperalgesic effect on mechanical hyperalgesia (paw pressure test) in rats induced by chronic constriction injury of the sciatic nerve was assessed after repeated administrations (five injections every half-life, a regimen close to clinical use). Naloxone administered at a dose of 1 mg/kg i.v., which blocks all opioid receptors, or at a low dose of 1 g/kg i.v., which selectively blocks the -opioid receptor, inhibited the antihyperalgesic effect of clomipramine and hence indicated that -opioid receptor is involved. Depending on whether they are administered by the intracerebroventricular or intrathecal route, specific antagonists of the various opioid receptor subtypes [D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH 2 (CTOP), ; naltrindole (NTI), ␦; and nor-binaltorphimine (nor-BNI), ] differently modify the antihyperalgesic effect of chronically injected clomipramine. The effect was inhibited by intrathecal administration of CTOP and intracerebroventricular administration of naltrindole, whereas nor-BNI was ineffective whatever the route of injection. These results demonstrate a differential involvement of opioid receptors according to the level of the central nervous system: ␦-receptors at the supraspinal level and -receptors at the spinal level. Clomipramine could act via a neuronal pathway in which these two receptors are needed.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Marchand

Ardid²,

Chapuy³

et al. 2003

J Pharmacol Exp Ther

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“…Similarly, serotonin antagonists decreased antinociception elicited by trazodone, implying a serotonergic mechanism of antinociception. The authors postulated an antinociceptive effect of trazodone because of the combined influences of the µ1-, µ2-opioid and serotonergic receptors [21]. The same group found a weak effect of fluvoxamine, an SSRI [22].…”

Section: Basis Of Use Of Antidepressants For Pain: Mechanisms Of Actionmentioning

confidence: 99%

Antidepressants for chronic neuropathic pain

Reisner

2003

Current Science Inc

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Tricyclic antidepressants have been used to manage pain for several decades, and are superior treatments for some patients suffering from neuropathic pain. Unfortunately, older antidepressants have dose-limiting side effects that can lead to drug intolerance. The most common are anticholinergic side effects, although some patients experience sexual dysfunction. Cognitive impairment, sedation, and orthostatic hypotension also are relatively common. Taking an overdose of tricyclic antidepressants can be lethal in overdose. Several weeks of therapy may be required before antinociception occurs, but tricyclic antidepressants in optimal doses appear to be the most effective treatment for neuropathic pain; this is supported by systematic reviews comparing them with other agents. Newer medications such as atypical antidepressants and anticonvulsants may be overtaking older antidepressants, but they should not be overlooked as important options for the management of pain.

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“…Trazodone and nefazodone also share an active metabolite, m-chlorophenylpiperazine (mCPP), which acts as a serotonin 5HT2C agonist and appears to be able to release serotonin presynaptically (Rothman and Baumann, 2002), while nefazodone also appears to act as a non-competitive antagonist of nicotinic acetylcholinergic receptors (Fryer and Lukas, 1999). Trazodone also appears to stimulate the µ1-and µ2-opioid receptors (Schreiber et al, 2000) and is a potent agonist of the serotonin 5HT2C receptors, which are able, when activated (Marcoli et al, 1998;Maura et al, 2000), to inhibit the N-methyl-D-aspartate (NMDA)-emergent cyclic GMP elevation. Since trazodone is also a weak inhibitor of serotonin reuptake, the overall effect of trazodone appears to be an increase in extracellular levels of serotonin in the brain (Pazzagli et al, 1999).…”

Section: Serotonin Receptor Antagonists/agonistsmentioning

confidence: 99%

Monoaminergic‐based Pharmacotherapy for Depression

Papakostas¹,

Fava²

2005

Biology of Depression

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Although recent advances in neuropharmacology, neuroendocrinology, molecular biology, and pharmacogenetics have been instrumental in bringing about potential treatments for depression which are fundamentally unrelated to their predecessors, including substance P antagonists, glutaminergic agents, and corticotropinreleasing factor (CRF) antagonists, nevertheless it was agents that influenced the function of monoamine receptors and transporters that were discovered initially by serendipity and then developed as treatments for depression. The development of such compounds also served as a framework for the understanding of depression as a medical illness affecting brain functioning. As a result of these efforts, our field has gained further understanding of the role of monoamines in depression. In previous chapters, the relevance of monoamines in the underlying pathophysiology of depression was reviewed. In the following chapter we will focus on describing the contemporary role of monoaminergic agents in the treatment of depression. 6.

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The antinociceptive effect of trazodone in mice is mediated through both μ-opioid and serotonergic mechanisms

Cited by 41 publications

References 23 publications

Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Antidepressants for chronic neuropathic pain

Monoaminergic‐based Pharmacotherapy for Depression

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