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Thomas Weiser - One of the best experts on this subject based on the ideXlab platform.
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Topical Ambroxol for the treatment of neuropathic pain
Der Schmerz, 2015Co-Authors: K.-u. Kern, Thomas WeiserAbstract:ZusammenfassungHintergrundNeuropathische Schmerzen sind schwer behandelbar, die vorhandenen Therapien oft nicht ausreichend. Das Sekretolytikum Ambroxol hat auch stark lokalanästhetische Eigenschaften und hemmt Natriumkanäle ca. 40 mal potenter als Lidocain. Es blockiert bevorzugt den Kanalsubtyp Na_v 1.8, der besonders in nozizeptiven C-Fasern exprimiert wird. Bei geringer Toxizität erschien ein Behandlungsversuch mit topischen Ambroxol berechtigt bei unzureichend behandelbaren, neuropathischen Schmerzen.Material und MethodeRetrospektiv werden exemplarisch 7 Krankheitsverläufe von Patienten mit schweren, neuropathischenSchmerzen dargestellt, bei denen viele Behandlungsversuche mit zugelassenen Substanzen erfolglos odernicht möglich waren. Diese waren in einem umschriebenen Areal topisch mit einer Ambroxol 20 %-Cremebehandelt worden.ErgebnisseSchmerzursachen waren: Postzosterneuralgie (2x), Mononeuropathia multiplex, Deafferenzierungsschmerz, Phantomschmerz, postoperative Neuralgie und unklare Fußneuropathie. Diedurchschnittlichen Schmerzstärken lagen zwischen 4–6/10 (NRS), maximal bei 6–10/10. DieSchmerzreduktionen unter Ambroxol betrugen 2–8 Punkte (NRS) binnen 15–30 min und hielten 3–8 h an.Schmerzattacken reduzierten sich bei allen 5 Betroffenen. 4 Patienten ohne vorherige Besserung auf Lidocain 5 % und 1 Patient ohne Linderung auf Capsaicin 8% profitierten dennoch von topischem Ambroxol. Kein Patient berichtete Nebenwirkungen oder Hautveränderungen, die längste Behandlung überblickt mittlerweile 4 Jahre.SchlussfolgerungAmbroxol wirkt als starkes Lokalanästhetikum und blockiert bevorzugt den nozizeptiv relevanten Kanalsubtyp Na_v 1.8. Wir berichten hier erstmals über eine relevante Schmerzlinderung durch topisches Ambroxol 20 % bei Patienten mit neuropathischem Schmerz. Angesichts des günstigen Nebenwirkungsprofils sollte der klinische Nutzen für Schmerzpatienten dringend weiter untersucht werden.AbstractBackgroundNeuropathic pain is difficult to treat, and the available options are often inadequate. The expectorant Ambroxol also acts as a strong local anaesthetic and blocks sodium channels about 40 times more potently than lidocaine. It preferentially inhibits the channel subtype Na_v 1.8, which is expressed especially in nociceptive C-fibres. In view of the low toxicity of Ambroxol, it seemed reasonable to try using it for the treatment of neuropathic pain that failed to respond to other standard options.Material and methodsThe medical records of seven patients with severe neuropathic pain and pain reduction following topical Ambroxol treatment are reported retrospectively. As standard therapies had not proved sufficient, a topical Ambroxol 20 % cream was repeatedly applied by the patients in the area of neuropathic pain.ResultsThe reasons for neuropathic pain were postherpetic neuralgia (2 ×), mononeuropathy multiplex, phantom pain, deafferentation pain, postoperative neuralgia and foot neuropathy of unknown origin. The individual mean pain intensity reported was between 4 and 6/10 (NRS), maximum pain at 6–10/10 (NRS). The pain reduction achieved individually following Ambroxol cream was 2–8 points (NRS) within 5–30 min and lasted for 3–8 h. Pain attacks were reduced in all five patients presenting with this problem. Four patients with no improvement after lidocaine 5 % and one patient with no response to capsaicin 8 % nevertheless experienced a pain reduction with topical Ambroxol. No patient reported any side effects or skin changes during a treatment that has since been continued for up to 4 years.ConclusionAmbroxol acts as a strong local anaesthetic and preferentially inhibits the nociceptively relevant sodium channel subtype Na_v 1.8. For the first time, we report below on a relevant pain relief following topical Ambroxol 20 % cream in patients with neuropathic pain. In view of the positive side effect profile, the clinical benefit in patients with pain should be investigated further.
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Topical Ambroxol for the treatment of neuropathic pain
Der Schmerz, 2015Co-Authors: K.-u. Kern, Thomas WeiserAbstract:Background Neuropathic pain is difficult to treat, and the available options are often inadequate. The expectorant Ambroxol also acts as a strong local anaesthetic and blocks sodium channels about 40 times more potently than lidocaine. It preferentially inhibits the channel subtype Na_v 1.8, which is expressed especially in nociceptive C-fibres. In view of the low toxicity of Ambroxol, it seemed reasonable to try using it for the treatment of neuropathic pain that failed to respond to other standard options. Material and methods The medical records of seven patients with severe neuropathic pain and pain reduction following topical Ambroxol treatment are reported retrospectively. As standard therapies had not proved sufficient, a topical Ambroxol 20 % cream was repeatedly applied by the patients in the area of neuropathic pain. Results The reasons for neuropathic pain were postherpetic neuralgia (2 ×), mononeuropathy multiplex, phantom pain, deafferentation pain, postoperative neuralgia and foot neuropathy of unknown origin. The individual mean pain intensity reported was between 4 and 6/10 (NRS), maximum pain at 6–10/10 (NRS). The pain reduction achieved individually following Ambroxol cream was 2–8 points (NRS) within 5–30 min and lasted for 3–8 h. Pain attacks were reduced in all five patients presenting with this problem. Four patients with no improvement after lidocaine 5 % and one patient with no response to capsaicin 8 % nevertheless experienced a pain reduction with topical Ambroxol. No patient reported any side effects or skin changes during a treatment that has since been continued for up to 4 years. Conclusion Ambroxol acts as a strong local anaesthetic and preferentially inhibits the nociceptively relevant sodium channel subtype Na_v 1.8. For the first time, we report below on a relevant pain relief following topical Ambroxol 20 % cream in patients with neuropathic pain. In view of the positive side effect profile, the clinical benefit in patients with pain should be investigated further. Hintergrund Neuropathische Schmerzen sind schwer behandelbar, die vorhandenen Therapien oft nicht ausreichend. Das Sekretolytikum Ambroxol hat auch stark lokalanästhetische Eigenschaften und hemmt Natriumkanäle ca. 40 mal potenter als Lidocain. Es blockiert bevorzugt den Kanalsubtyp Na_v 1.8, der besonders in nozizeptiven C-Fasern exprimiert wird. Bei geringer Toxizität erschien ein Behandlungsversuch mit topischen Ambroxol berechtigt bei unzureichend behandelbaren, neuropathischen Schmerzen. Material und Methode Retrospektiv werden exemplarisch 7 Krankheitsverläufe von Patienten mit schweren, neuropathischenSchmerzen dargestellt, bei denen viele Behandlungsversuche mit zugelassenen Substanzen erfolglos odernicht möglich waren. Diese waren in einem umschriebenen Areal topisch mit einer Ambroxol 20 %-Cremebehandelt worden. Ergebnisse Schmerzursachen waren: Postzosterneuralgie (2x), Mononeuropathia multiplex, Deafferenzierungsschmerz, Phantomschmerz, postoperative Neuralgie und unklare Fußneuropathie. Diedurchschnittlichen Schmerzstärken lagen zwischen 4–6/10 (NRS), maximal bei 6–10/10. DieSchmerzreduktionen unter Ambroxol betrugen 2–8 Punkte (NRS) binnen 15–30 min und hielten 3–8 h an.Schmerzattacken reduzierten sich bei allen 5 Betroffenen. 4 Patienten ohne vorherige Besserung auf Lidocain 5 % und 1 Patient ohne Linderung auf Capsaicin 8% profitierten dennoch von topischem Ambroxol. Kein Patient berichtete Nebenwirkungen oder Hautveränderungen, die längste Behandlung überblickt mittlerweile 4 Jahre. Schlussfolgerung Ambroxol wirkt als starkes Lokalanästhetikum und blockiert bevorzugt den nozizeptiv relevanten Kanalsubtyp Na_v 1.8. Wir berichten hier erstmals über eine relevante Schmerzlinderung durch topisches Ambroxol 20 % bei Patienten mit neuropathischem Schmerz. Angesichts des günstigen Nebenwirkungsprofils sollte der klinische Nutzen für Schmerzpatienten dringend weiter untersucht werden.
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Ambroxol: A CNS Drug?
CNS neuroscience & therapeutics, 2008Co-Authors: Thomas WeiserAbstract:For almost three decades Ambroxol has been used in the therapy of airway diseases. In 2002, Ambroxol lozenges were marketed for the treatment of sore throat making use of its local anesthetic effect. Detailed investigations of Ambroxol with modern pharmacological methods yielded additional interesting results: Ambroxol has been found to have profound effects on neuronal voltage-gated Na+, as well as Ca2+ channels, and to effectively reduce chronic inflammatory and neuropathic pain in rodents. The question was raised whether Ambroxol affects the central nervous system (CNS) directly, or whether its effects can be explained solely by a peripheral action. This issue was addressed by reexamining pharmacokinetics, as well as toxicology of Ambroxol. It has been concluded that even at the highest clinically used doses Ambroxol does not have significant direct effects on the CNS. At clinically relevant plasma concentrations Ambroxol either does not penetrate blood-brain barrier, or its brain levels are too low to cause relevant effects. The analgesic effects of Ambroxol by either systemic administration to animals, or by topical application in humans can be explained by Ambroxol-induced blockade of ion channels in peripheral neurons.
Yindi Zhang - One of the best experts on this subject based on the ideXlab platform.
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simultaneous determination and pharmacokinetic study of roxithromycin and Ambroxol hydrochloride in human plasma by lc ms ms
Clinica Chimica Acta, 2007Co-Authors: Taijun Hang, Meng Zhang, Min Song, Jianping Shen, Yindi ZhangAbstract:Abstract Background Although roxithromycin and Ambroxol HCl were often administered concomitantly for the treatment of respiratory infections, the pharmacokinetic interactions between them have not been reported. We investigated the interactions between these drugs in health male Chinese volunteers by LC-MS/MS in human plasma. Methods The pharmacokinetics were studied in 12 healthy male Chinese volunteers after an overnight fast by a single oral dose, 4-way crossover design with a period of 7-day washout. Each subjects was randomized to receive a single oral dose of 1 compound roxithromycin (150 mg) and Ambroxol HCl (30 mg) dispersible tablet (test formulation, treatment A), one 150 mg roxithromycin dispersible tablet together with one 30 mg Ambroxol HCl tablet (combined reference formulations, treatment B), one 150 mg roxithromycin dispersible tablet (reference formulation I, treatment C), or one 30 mg Ambroxol HCl tablet (reference formulation II, treatment D) with 250 ml of water. Venous blood was collected at pre-dose (0 h) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72 h after dosing. The plasma concentrations of roxithromycin and Ambroxol HCl were simultaneously determined by using a validated internal standard LC-MS/MS method. Results No significant differences were observed for the major pharmacokinetic parameters such as Cmax, Tmax, t1/2 and AUC of both roxithromycin and Ambroxol HCl between different treatments. Conclusion The pharmacokinetics of both roxithromycin and Ambroxol HCl are not affected by their concomitant oral administration. Therefore, there are no obvious pharmacokinetic interactions between roxithromycin and Ambroxol HCl after oral administration. Roxithromycin and Ambroxol HCl dispersible tablets were bioequivalent with reference to the roxithromycin dispersible tablets and Ambroxol HCl tablets in combination usage.
Tadeusz Pietras - One of the best experts on this subject based on the ideXlab platform.
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Protective effect of Ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice
The European respiratory journal, 1994Co-Authors: Dariusz Nowak, Adam Antczak, Tadeusz Pietras, Piotr Białasiewicz, Maciej KrolAbstract:We wanted to determine whether Ambroxol, a drug which stimulates the release of surfactant by type II pneumocytes, can protect lung lipids from peroxidative damage in mice. Animals were injected intraperitoneally with Ambroxol, 0.169 mmol.kg-1, or 1 ml buffer once a day for three consecutive days. Lipid peroxidation was then induced in lung homogenates either by means of heat, 50 degrees C, or H2O2, 10 mmol.l-1. The lung homogenates from Ambroxol-treated animals revealed decreased lipid peroxidation in response to both stimuli. The heat- and H2O2-induced generation of conjugated dienes (a first lipid peroxidation product) in Ambroxol-treated lung homogenates was 3.7 and 3.1 fold lower than in the lungs from buffer-injected mice. Ambroxol, as an inhibitor of heat- and H2O2-induced lipid peroxidation, was equipotent to and stronger than the two antioxidants, N-acetylcysteine and methionine, respectively. Ambroxol was not able to protect heart and liver lipids. These results suggest that Ambroxol can sufficiently enhance the antioxidant defence in lung tissue and can act as a lung lipid antioxidant.
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Antioxidant properties of Ambroxol
Free radical biology & medicine, 1994Co-Authors: Dariusz Nowak, Adam Antczak, Piotr Białasiewicz, Maciej Krol, Tadeusz PietrasAbstract:We tested whether Ambroxol, a drug which stimulates the release of surfactant by pneumocytes type II, may also possess antioxidant properties. To assess the reactivity of Ambroxol with reactive oxygen species, we analysed its ability to decompose hydrogen peroxide (H2O2) and to inhibit the superoxide (O2.-)-dependent autooxidation of pyrogallol, hydroxyl radical (.OH)-mediated deoxyribose oxidation, and hypochlorous acid (HClO-induced chlorination of monochlorodimedon. Ambroxol was found to be a sufficient scavenger of HClO and .OH and also revealed the capacity to decompose H2O2. At concentrations of 25 and 70 microM, it inhibited HClO-induced chlorination of monochlorodimedon by 22 +/- 13 and 59 +/- 14%, respectively. Similarly, at concentrations of 1, 2, and 10 mM, Ambroxol decreased .OH-mediated deoxyribose oxidation by 47 +/- 11, 75 +/- 9, and 89 +/- 4%. In addition, at concentrations of 1 to 5 mM, it completely protected linoleic acid from .OH-induced peroxidative damage. Ambroxol had a weak effect on O2.(-)-dependent autooxidation of pyrogallol. Our results indicate that Ambroxol has antioxidant activity, which may have clinical significance in protecting lung tissue from oxidant-induced injury.
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Ambroxol inhibits endotoxin-induced lipid peroxidation in mice.
Polish journal of pharmacology, 1993Co-Authors: Dariusz Nowak, Adam Antczak, Tadeusz Pietras, Maciej Krol, G. PiaseckaAbstract:Administration of Ambroxol (70 mg/kg ip) once a day for 3 days protected lung and heart lipids from lipopolysaccharide (LPS, 17 mg/kg)-induced oxidative stress in mice. Ambroxol as a lipid peroxidation inhibitor was almost as active as an equivalent dose of N-acetylcysteine (27.6 mg/kg), a well known antioxidant. The lung and heart levels of conjugated dienes in animals pretreated with Ambroxol were 3.3- and 1.7-times lower (p < 0.05 and p < 0.01) than those observed in the control group which received only buffer and subsequently LPS. These results indicate that Ambroxol can sufficiently inhibit the harmful process of lipid peroxidation in vivo.
Dariusz Nowak - One of the best experts on this subject based on the ideXlab platform.
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Protective effect of Ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice
The European respiratory journal, 1994Co-Authors: Dariusz Nowak, Adam Antczak, Tadeusz Pietras, Piotr Białasiewicz, Maciej KrolAbstract:We wanted to determine whether Ambroxol, a drug which stimulates the release of surfactant by type II pneumocytes, can protect lung lipids from peroxidative damage in mice. Animals were injected intraperitoneally with Ambroxol, 0.169 mmol.kg-1, or 1 ml buffer once a day for three consecutive days. Lipid peroxidation was then induced in lung homogenates either by means of heat, 50 degrees C, or H2O2, 10 mmol.l-1. The lung homogenates from Ambroxol-treated animals revealed decreased lipid peroxidation in response to both stimuli. The heat- and H2O2-induced generation of conjugated dienes (a first lipid peroxidation product) in Ambroxol-treated lung homogenates was 3.7 and 3.1 fold lower than in the lungs from buffer-injected mice. Ambroxol, as an inhibitor of heat- and H2O2-induced lipid peroxidation, was equipotent to and stronger than the two antioxidants, N-acetylcysteine and methionine, respectively. Ambroxol was not able to protect heart and liver lipids. These results suggest that Ambroxol can sufficiently enhance the antioxidant defence in lung tissue and can act as a lung lipid antioxidant.
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Antioxidant properties of Ambroxol
Free radical biology & medicine, 1994Co-Authors: Dariusz Nowak, Adam Antczak, Piotr Białasiewicz, Maciej Krol, Tadeusz PietrasAbstract:We tested whether Ambroxol, a drug which stimulates the release of surfactant by pneumocytes type II, may also possess antioxidant properties. To assess the reactivity of Ambroxol with reactive oxygen species, we analysed its ability to decompose hydrogen peroxide (H2O2) and to inhibit the superoxide (O2.-)-dependent autooxidation of pyrogallol, hydroxyl radical (.OH)-mediated deoxyribose oxidation, and hypochlorous acid (HClO-induced chlorination of monochlorodimedon. Ambroxol was found to be a sufficient scavenger of HClO and .OH and also revealed the capacity to decompose H2O2. At concentrations of 25 and 70 microM, it inhibited HClO-induced chlorination of monochlorodimedon by 22 +/- 13 and 59 +/- 14%, respectively. Similarly, at concentrations of 1, 2, and 10 mM, Ambroxol decreased .OH-mediated deoxyribose oxidation by 47 +/- 11, 75 +/- 9, and 89 +/- 4%. In addition, at concentrations of 1 to 5 mM, it completely protected linoleic acid from .OH-induced peroxidative damage. Ambroxol had a weak effect on O2.(-)-dependent autooxidation of pyrogallol. Our results indicate that Ambroxol has antioxidant activity, which may have clinical significance in protecting lung tissue from oxidant-induced injury.
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Ambroxol inhibits endotoxin-induced lipid peroxidation in mice.
Polish journal of pharmacology, 1993Co-Authors: Dariusz Nowak, Adam Antczak, Tadeusz Pietras, Maciej Krol, G. PiaseckaAbstract:Administration of Ambroxol (70 mg/kg ip) once a day for 3 days protected lung and heart lipids from lipopolysaccharide (LPS, 17 mg/kg)-induced oxidative stress in mice. Ambroxol as a lipid peroxidation inhibitor was almost as active as an equivalent dose of N-acetylcysteine (27.6 mg/kg), a well known antioxidant. The lung and heart levels of conjugated dienes in animals pretreated with Ambroxol were 3.3- and 1.7-times lower (p < 0.05 and p < 0.01) than those observed in the control group which received only buffer and subsequently LPS. These results indicate that Ambroxol can sufficiently inhibit the harmful process of lipid peroxidation in vivo.
Maciej Krol - One of the best experts on this subject based on the ideXlab platform.
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Protective effect of Ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice
The European respiratory journal, 1994Co-Authors: Dariusz Nowak, Adam Antczak, Tadeusz Pietras, Piotr Białasiewicz, Maciej KrolAbstract:We wanted to determine whether Ambroxol, a drug which stimulates the release of surfactant by type II pneumocytes, can protect lung lipids from peroxidative damage in mice. Animals were injected intraperitoneally with Ambroxol, 0.169 mmol.kg-1, or 1 ml buffer once a day for three consecutive days. Lipid peroxidation was then induced in lung homogenates either by means of heat, 50 degrees C, or H2O2, 10 mmol.l-1. The lung homogenates from Ambroxol-treated animals revealed decreased lipid peroxidation in response to both stimuli. The heat- and H2O2-induced generation of conjugated dienes (a first lipid peroxidation product) in Ambroxol-treated lung homogenates was 3.7 and 3.1 fold lower than in the lungs from buffer-injected mice. Ambroxol, as an inhibitor of heat- and H2O2-induced lipid peroxidation, was equipotent to and stronger than the two antioxidants, N-acetylcysteine and methionine, respectively. Ambroxol was not able to protect heart and liver lipids. These results suggest that Ambroxol can sufficiently enhance the antioxidant defence in lung tissue and can act as a lung lipid antioxidant.
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Antioxidant properties of Ambroxol
Free radical biology & medicine, 1994Co-Authors: Dariusz Nowak, Adam Antczak, Piotr Białasiewicz, Maciej Krol, Tadeusz PietrasAbstract:We tested whether Ambroxol, a drug which stimulates the release of surfactant by pneumocytes type II, may also possess antioxidant properties. To assess the reactivity of Ambroxol with reactive oxygen species, we analysed its ability to decompose hydrogen peroxide (H2O2) and to inhibit the superoxide (O2.-)-dependent autooxidation of pyrogallol, hydroxyl radical (.OH)-mediated deoxyribose oxidation, and hypochlorous acid (HClO-induced chlorination of monochlorodimedon. Ambroxol was found to be a sufficient scavenger of HClO and .OH and also revealed the capacity to decompose H2O2. At concentrations of 25 and 70 microM, it inhibited HClO-induced chlorination of monochlorodimedon by 22 +/- 13 and 59 +/- 14%, respectively. Similarly, at concentrations of 1, 2, and 10 mM, Ambroxol decreased .OH-mediated deoxyribose oxidation by 47 +/- 11, 75 +/- 9, and 89 +/- 4%. In addition, at concentrations of 1 to 5 mM, it completely protected linoleic acid from .OH-induced peroxidative damage. Ambroxol had a weak effect on O2.(-)-dependent autooxidation of pyrogallol. Our results indicate that Ambroxol has antioxidant activity, which may have clinical significance in protecting lung tissue from oxidant-induced injury.
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Ambroxol inhibits endotoxin-induced lipid peroxidation in mice.
Polish journal of pharmacology, 1993Co-Authors: Dariusz Nowak, Adam Antczak, Tadeusz Pietras, Maciej Krol, G. PiaseckaAbstract:Administration of Ambroxol (70 mg/kg ip) once a day for 3 days protected lung and heart lipids from lipopolysaccharide (LPS, 17 mg/kg)-induced oxidative stress in mice. Ambroxol as a lipid peroxidation inhibitor was almost as active as an equivalent dose of N-acetylcysteine (27.6 mg/kg), a well known antioxidant. The lung and heart levels of conjugated dienes in animals pretreated with Ambroxol were 3.3- and 1.7-times lower (p < 0.05 and p < 0.01) than those observed in the control group which received only buffer and subsequently LPS. These results indicate that Ambroxol can sufficiently inhibit the harmful process of lipid peroxidation in vivo.