Local Anesthetic Properties of a Novel Derivative, N-Methyl Doxepin, Versus Doxepin and Bupivacaine

Sudoh, Yukari; Cahoon, Elaine Elliott; Girolami, Umberto De; Wang, Ging Kuo

doi:10.1213/01.ane.0000100742.87447.c1

Cited by 20 publications

(7 citation statements)

References 14 publications

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“…Recently, the first antidepressant (Duloxetine), administered as a capsule comprising enteric coated pellets, has been approved for the management of diabetic peripheral neuropathic pain [6]. Amitriptyline, doxepin and imipramine (drugs that nonselectively block the reuptake of monoamines) appear to express the most potent analgesic effect [4], and its chronic use seems to be safe and effective [7], even more that other local anesthetics like bupivacaine or lidocaine [1,[8][9][10]. Intrathecal amitriptyline reverses thermal hyperalgesia induced by carrageenan in a dose-dependent manner [11] and given systemically, the drug is effective in alleviating thermal hyperalgesia induced by spinal nerve ligation [12].…”

Section: Introductionmentioning

confidence: 99%

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

García¹,

Escribano²,

Colom³

et al. 2011

CNANO

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Tricyclic antidepressants (TCAs) have potent local pain blockade properties that could be of interest in relieving chronic pain states as neuropathic pain. The aim of this work was to reach a persistent control of nociceptive and neuropathic pain by means of an injectable controlled release system using lower than usual doses of TCAs. To address this issue, amitriptyline, doxepin and imipramine were encapsulated with poly (lactic-co-glycolic) acid (PLGA) as polymer. Nanoparticles were characterized. The in vitro drug release profile and mechanism was evaluated, and the in vivo analgesic and anti-allodynic activity in front of heat-induced nociceptive pain and sciatic nerve chronic constriction injury, respectively, was tested. The mean±SD particle size and drug loadings (%) of the nanoparticles obtained were 420±13, 480±73 and 373±25nm, and 40.46±4.11, 31.09±3.02 and 32.20±3.20 % for amitriptyline, doxepin and imipramine, respectively. According to the Korsmeyer-Peppas model, the release mechanism of doxepin was diffusion controlled, while a combination of Fickian diffusion and polymer relaxation/erosion of the PLGA matrix was involved for amitriptyline and imipramine. After local infiltration of nanoparticles in rats, the antinociceptive and anti-allodynic activity of the encapsulated drugs were long-lasting and higher than that observed from the solutions. Amitriptyline elicited the lower analgesic effect. Doxepin showed the most outstanding results and its encapsulation led to a 62% and 229% increase in antinociceptive and anti-allodynic activity, respectively. So, this drug could be considered as a therapeutical alternative in pain relieving treatments.

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Section: Introductionmentioning

confidence: 99%

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

García¹,

Escribano²,

Colom³

et al. 2011

CNANO

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“…[5][6][7][8][9][10] However, various studies on a range of other quaternary cationic compounds have shown that these can block electrical conductances in axons when applied outside of the cell. Such studies involved QX-572, 11,12 quaternary tropine esters, 7,13 tonicaine, 14 -16 quaternary derivatives of amitriptyline [17][18][19] and doxepin, 17,20 and methyl and benzyl quaternary derivatives of novocaine, cocaine, dibucaine, and tetracaine. 21 In addition, there are preliminary in vitro 5,8,22,23 and in vivo 16,23 data to suggest that extracellular QX-314 can, in fact, affect action potentials, although these findings were not further pursued with regard to their potential clinical local anesthetic utility.…”

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confidence: 99%

The Quaternary Lidocaine Derivative, QX-314, Produces Long-lasting Local Anesthesia in Animal Models In Vivo

Lim¹,

MacLeod²,

Ries

et al. 2007

Anesthesiology

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In a randomized, controlled laboratory study, the quaternary lidocaine derivative, QX-314, concentration-dependently and reversibly produced long-lasting local anesthesia with a slow onset in animal models in vivo. The authors' results raise the possibility that quaternary ammonium compounds may produce clinically useful local anesthesia of long duration in humans and challenge the conventional notion that these agents are ineffective when applied extracellularly.

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“…The use of tricyclics has been shown to result in increased serotonin and norepinephrine in neuronal synapses, both of which may affect mood and pain sensation. Tricyclics are also potent sodium channel blockers [94] and have been shown to inhibit spinal N-methyl-daspartate receptors as well. Its peripheral activity may occur at the adenosine-, H1-, and H2-receptors as well as via enkephalin-like activity.…”

Section: Anestheticsmentioning

confidence: 99%

Management of radiation therapy-induced mucositis in head and neck cancer patients. Part II: supportive treatments

2008

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Oropharyngeal mucositis is the acute inflammatory and ulcerative reaction of the oral mucosa following radiation therapy to the head and neck region. It is such a common problem that nearly all head and neck cancer patients develop some degree of mucositis. This complication is usually transient in nature but it also represents an important clinical problem as it is a painful, debilitating, dose-dependent side effect for which there is no widely acceptable prophylaxis or effective treatment. As several authoritative groups have recently either undertaken systematic reviews or issued guidelines on the management of mucositis, it is the aim of this review instead, to provide an overview of all the remedies and pharmaceutical agents available, as well as highlighting to researchers the gaps that need to be filled.

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Local Anesthetic Properties of a Novel Derivative, N-Methyl Doxepin, Versus Doxepin and Bupivacaine

Abstract: N-methyl doxepin and doxepin are both potent Na(+) channel blockers; they elicit rat sciatic nerve block lasting longer than that induced by bupivacaine and seem to be nontoxic to peripheral nerves at concentrations up to 10 mM.

Cited by 20 publications

References 14 publications

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

The Quaternary Lidocaine Derivative, QX-314, Produces Long-lasting Local Anesthesia in Animal Models In Vivo

Management of radiation therapy-induced mucositis in head and neck cancer patients. Part II: supportive treatments

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