Competitive and open channel block of recombinant nAChR channels by different antibiotics

Schlesinger, Friedrich; Kenn, Klaus; Haeseler, Gertrud; Dengler, Reinhard; Bufler, J.

doi:10.1016/j.nmd.2004.01.005

Cited by 18 publications

(7 citation statements)

References 27 publications

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“…In their study [25], open channel block was observed at a high concentration of gentamicin (10 mM) and calcium almost completely restored the tetanic tension; therefore, it seems that open channel block caused by gentamicin would probably not have contributed to the increasing tetanic fade seen in our study. An increased calcium concentration enhances acetylcholine release at the nerve terminal and results in increased acetylcholine concentration in the synaptic cleft.…”

Section: Discussionsupporting

confidence: 46%

“…Schlesinger et al [25] demonstrated that gentamicin could cause competitive inhibition and open ion channel block of the nAChR channel complex at the end-plate. In their study [25], open channel block was observed at a high concentration of gentamicin (10 mM) and calcium almost completely restored the tetanic tension; therefore, it seems that open channel block caused by gentamicin would probably not have contributed to the increasing tetanic fade seen in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Decreased acetylcholine release at the nerve terminal [1,2] and the competitive inhibition of nAChR at the end-plate [25], or maybe at the nerve terminal, may be important mechanisms underlying the impairment of neuromuscular transmission caused by gentamicin.…”

Section: Discussionmentioning

confidence: 99%

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Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations

Lee

et al. 2008

J Anesth

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

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Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations

Lee

et al. 2008

J Anesth

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“…The maximum therapeutic levels of kanamycin, lincomycin, gentamicin, streptomycin, tobramycin, amikacin, and neomycin interrupted neuromuscular transmission, which is acknowledged as a realistic measure of possible clinical neuromuscular blockade. Moreover, Schlesinger et al [26] reported that the half-maximal blocking concentration is within a clinically relevant concentration or close to it. Potter et al [17] also reported that gentamicin increased the blocking effect of d-tubocurarine when administered to cats at a therapeutic dose of 1 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

The synergistic effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade

Lee

Chung

et al. 2013

Korean J Anesthesiol

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BackgroundGentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs.MethodsMale Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity.ResultsThe administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions.ConclusionsThis study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.

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“…Doxycycline is one of the most extensively studied for properties other than its antimicrobial effects (Aminov, 2013;Chen et al, 2019;Stephenson et al, 2018), and excellent blood-brain barrier permeability (Barza et al, 1975;Liu et al, 2001). The drug is known to have a broad range of actions (Garrido-Mesa et al, 2013) including the modification of the neurotransmitters system known to be involved in the pathophysiology of LID such as the cholinergic (Conti et al, 2018;Schlesinger et al, 2004;Schlesinger et al, 2004), serotonergic (Zhang et al, 2006), glutamatergic (Monte et al, 2013) as well as others (Mansson et al, 2007;Munzar et al, 2002). In addition, González-Lizárraga et al (2017) reported that doxycycline reshapes α-synuclein oligomers, inhibits α-synuclein aggregation, and the seeding of new oligomers, thus preventing cytotoxicity in dopaminergic cell lines.…”

Section: Antimicrobial Drugs In Parkinson's Diseasementioning

confidence: 99%

Doxycycline, an anti-inflammatory agent, alleviates dyskinesia induced by L-DOPA in Parkinsonian rats

Bortolanza¹,

Nascimento²,

Raisman‐Vozari³

et al. 2020

Preprint

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Background and Purpose L-DOPA induced dyskinesia is a debilitating side effect of treating Parkinson's disease with L-DOPA. There is a need to discover a treatment that has the same benefits as L-DOPA treatment without the associated side effects. Here, we demonstrate the anti-dyskinetic potential of doxycycline and the analog compound COL-3 (without antimicrobial activity) in hemiparkinsonian rats presenting L-DOPA-induced dyskinesia. Experimental Approach Wistar adult male rats received a unilateral medial forebrain bundle injection of 6-hydroxydopamine and were then orally administered L-DOPA once a day for 14 days. This resulted in dyskinetic-like behavior. Key Results A single injection of doxycycline (intraperitoneal) or COL-3 (intracerebroventricular) together with L-DOPA attenuated the dyskinesia. Co-treatment with doxycycline from the first day of L-DOPA suppressed the onset of dyskinesia. The improved motor responses to L-DOPA remained intact in the presence of doxycycline or COL-3, indicating the preservation of the L-DOPA benefits. Doxycycline treatment was associated with decreased expression of FosB, cyclooxygenase-2, astrocytes, and microglia, which had previously been found to be elevated in the basal ganglia of rats exhibiting dyskinesia. In addition, metalloproteinase-2/-9 activity, metalloproteinase-3 expression, and production of reactive oxygen species in the basal ganglia of dyskinetic rats showed a significant positive correlation with the intensity of dyskinesia, which was decreased with the doxycycline treatment. Conclusion and Implications Given the longestablished and safe use of doxycycline and the similar effect of COL-3 (without antimicrobial activity), this study indicates that both drugs should undergo testing for their ability to reduce signs of dyskinesia induced by L-DOPA in patients with Parkinson's disease. Bullet point summary:'What is already known', Repeated treatment with L-DOPA induces dyskinesia (LID) in patients with Parkinson's disease (PD). Doxycycline is a clinically used antibiotic that posses dopamine neuroprotective properties and antiinflammatory activity.

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Competitive and open channel block of recombinant nAChR channels by different antibiotics

Cited by 18 publications

References 27 publications

Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations

Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations

The synergistic effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade

Doxycycline, an anti-inflammatory agent, alleviates dyskinesia induced by L-DOPA in Parkinsonian rats

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