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PubMed1994

Neomycin metabolism in calves.

Disposition of oral neomycin in calves was determined using 14C-labeled neomycin. The influences of age, diet, and method of administration were observed. All calves were killed 96 h after a single oral dose of [14C]neomycin (approximately 30 mg/kg) and the distribution of 14C in excreta and tissues was determined. As indicated by urinary excretion, absorption of neomycin was greater in 3-d-old calves (11.1 +/- 1.8% of the dose) than in 54- to 64-d-old nonruminating calves (1.5 +/- .58% of the dose) dosed similarly. Absorption of neomycin was similar in nonruminating (1.5 +/- .58%) and ruminating (2.13 +/- .62%) calves when the doses were administered in solution via a nippled bottle. In ruminating calves, absorption was somewhat less when the dose was administered on feed via a gelatin capsule (.5 +/- .06% of the dose) than when given in solution via a nippled bottle (2.13 +/- .62% of the dose). In calves dosed at 3 d of age, 14C concentration in the kidneys represented 55 +/- 4.9 ppm of neomycin equivalents. The next highest concentration occurred in the livers, which contained less than 5% of the level in kidneys. Tissue concentrations of 14C were related to absorption (as indicated by urinary excretion). Isolation and characterization (positive-ion fast atom bombardment mass spectroscopy and nuclear magnetic resonance spectroscopy) of 14C compounds in kidneys of calves dosed at 3 d of age indicated that at least 90% of the 14C was present as neomycin. Neomycin was also the major 14C compound in feces of all calves (70 to 80% of the 14C present).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Chemotherapy for giardiasis: randomized clinical trial of bacitracin, bacitracin zinc, and a combination of bacitracin zinc with neomycin.

This study describes a prospective, randomized, clinical trial in patients infected with the protozoa Giardia lamblia. Patients received a 10-day treatment with twice a day doses of either 120,000 U (USP) of bacitracin zinc, 120,000 U (USP) of bacitracin, 120,000 U (USP) of neomycin, or 60,000 U (USP) of bacitracin zinc and 60,000 U (USP) of neomycin. At the first assessment (day 11), all 21 subjects (100%) treated with bacitracin zinc had ceased to show Giardia parasites in their stools compared with 19 (95%) of 20 receiving bacitracin, 20 (90.9%) of 22 subjects receiving neomycin, and 17 (89.5%) of 19 subjects receiving bacitracin zinc plus neomycin. During the two-week follow up period, one (5.3%) of the 19 subjects examined who received bacitracin zinc experienced a recurrence compared with one (6.7%) of 15 receiving bacitracin, one (5.0%) of 20 receiving neomycin, and 0 (0%) of 14 receiving the combination treatment. Final cure rates of 94.7% for bacitracin zinc, 87.5% for bacitracin, 86.4% for neomycin, and 87.5% for bacitracin zinc plus neomycin were obtained. No synergistic activity was noted between bacitracin zinc and neomycin. Side effects were generally limited to nausea, abdominal discomfort, and diarrhea in a small number of patients.

Adolescent↗
PubMed1977

The effects of neomycin upon transmitter release and action.

These experiments were designed to determine the site and mechanism of action of neomycin on cholinergic transmission. These agents depressed the response of rat diaphragm preparations to phrenic nerve stimulation and to injected acetylcholine (ACh); however, equi-effective neuromuscular blocking concentrations of neomycin (6 x 10(-4) M), streptomycin (1.2 x 10(-3) M) or d-tubocurarine (6.5 x 10(-7) M) reduced the muscle response to injected ACh to 54,27 and 15% of control, respectively, suggesting that neomycin and streptomycin have a presynaptic effect. This finding was confirmed by measuring ACh release from the diaphragm during phrenic nerve stimulation; neomycin (6x10(-4) M) and streptomycin (1.2 x 10(-4) M) depressed ACh release to 29 and 41% of control, respectively. In the cat superior cervical ganglion neomycin (2 x 10(-3) M) blocked ganglionic transmission, did not reduce the response of ganglion cells to injected nicotine and depressed ACh release during preganglionic nerve stimulation to 61% of control in normal Ca++ (2.5 mM) medium and to less than 10% of control in low Ca++ (0.5 mM) medium. The increased accululation of 45Ca induced in rat isolated ganglia by preganglionic nerve stimulation was not changed by d-tubocurarine (2 x 10(-4) M), but was abolished by neomycin (2 x10(-3) M). It is concluded that neomycin blocks ACh release by blocking the influx of Ca++ necessary for transmitter release. This conclusion suggested that neomycin should block noradrenaline release, and this was shown using the anococcygeus preparation from the rat.

Acetylcholine↗
PubMed1983

[Standardization of the index of biological activity of the multi-component antibiotic neomycin].

The characteristic features of determination of the biological activity of neomycin and its separate components A, B and C were studied. Different sensitivity of 5 test microbes to neomycins A, B and C was observed. Bac. subtilis ATCC 6633 and Bac. cereus, var. myc. 537 were the most sensitive to neomycin A. Sar. lutea were not sensitive to neomycins A and C. The diffusion capacity of neomycin A was shown to be different from that of neomycins B and C. Even minute admixtures of neomycin A in the preparations of neomycin significantly changes the dose-response curves and affected the results of the biological activity determination.

Diffusion↗
PubMed1994

[Effects of neomycin on intestinal digestion, absorption and fermentation of carbohydrates in patients with liver cirrhosis: evidence for an alternative therapeutic mechanism in hepatic encephalopathy].

BACKGROUND: Despite non absorbable antibiotics and neomycin may have antagonistic effects on intestinal bacterial environment, both have synergistic effects in the treatment of hepatic encephalopathy. This could be due to their action on different enteric flora or a neomycin induced carbohydrate malabsorption. AIM: To investigate the effects of neomycin on intestinal digestion, absorption and fermentation of carbohydrates in patients with liver cirrhosis. PATIENTS AND METHODS: Thirty eight Child B or C cirrhotic patients separated in three groups; subjects within each group were randomized to receive neomycin (2/g/day for 10 days, n = 8) or placebo (n = 4). Absorption of lactose and d-xylose and fermentation of d-xylose, lactose and lactulose (measured using hydrogen breath tests) were studied before and after the treatment period. RESULTS: Neomycin did not change lactose fermentation but reduced plasma glucose rise after lactose ingestion (38.8 +/- mg/dl to 22 +/- 6 mg/dl p < 0.05). Plasma d-xylose levels at 30 min and its 5 h urinary excretion were reduced by neomycin from 19 +/- 3 to 9 +/- 2 mg/dl and from 4.9 +/- 0, 8 to 2.6 +/- 0.3 g/5h respectively (p < 0.05). Fermentation of d-xylose, lactose and lactulose was not reduced by neomycin. No significant changes were observed after placebo treatment. CONCLUSIONS: Neomycin therapy is associated with a reduction of intestinal digestion and absorption of carbohydrates, preserving bacterial fermentation capacity, probably increasing the non absorbable carbohydrate load reaching the colon.

Carbohydrate Metabolism↗
PubMed1996

Neomycin inhibits secretion of apolipoprotein[a] by increasing retention on the hepatocyte cell surface.

Neomycin therapy reduces plasma levels of low density lipoprotein and lipoprotein[a] (Lp[a]). To determine whether neomycin directly alters the biogenesis of Lp[a], we have examined the effect of neomycin on apolipoprotein[a] (apo[a]) synthesis and secretion in primary cultures of baboon hepatocytes. Using this system, we have previously shown that apo[a] is synthesized as a lower molecular weight precursor that upon maturation becomes associated with the cell surface before release into the culture medium. Treatment of hepatocytes with 10 mM neomycin reduced levels of apo[a] in the culture medium by as much as 12-fold. Although a portion of the reduced secretion could be accounted for by a reduction in total protein synthesis, the greatest effect of neomycin on apo[a] secretion was to decrease the release of mature apo[a] from the hepatocyte cell surface into the culture medium. Treatment of hepatocyte cultures with trypsin confirmed that mature apo[a] in neomycin-treated cells was still transported to the cell surface. Examination of related antibiotics demonstrated that inhibition of apo[a] secretion is a general property shared by the deoxystreptamine antibiotics. The mechanism by which neomycin affects the apo[a]-cell surface interaction is not known, but neomycin is known to perturb cell surface membranes, inhibit the interaction of some ligands with their cell surface receptors, and inhibit the metabolism of phosphatidylinositol 4,5 biphosphate. These studies suggest that cell surface association of apo[a] may play a role in Lp[a] biogenesis in vivo.

Animals↗
PubMed1998

Antibiotic inhibition of RNA catalysis: neomycin B binds to the catalytic core of the td group I intron displacing essential metal ions.

The aminoglycoside antibiotic neomycin B induces misreading of the genetic code during translation and inhibits several ribozymes. The self-splicing group I intron derived from the T4 phage thymidylate synthase (td) gene is one of these. Here we report how neomycin B binds to the intron RNA inhibiting splicing in vitro. Footprinting experiments identified two major regions of protection by neomycin B: one in the internal loop between the stems P4 and P5 and the other in the catalytic core close to the G-binding site. Mutational analyses defined the latter as the inhibitory site. Splicing inhibition is strongly dependent on pH and Mg2+ concentration, suggesting electrostatic interactions and competition with divalent metal ions. Fe2+-induced hydroxyl radical (Fe-OH.) cleavage of the RNA backbone was used to monitor neomycin-mediated changes in the proximity of the metal ions. Neomycin B protected several positions in the catalytic core from Fe-OH. cleavage, suggesting that metal ions are displaced in the presence of the antibiotic. Mutation of the bulged nucleotide in the P7 stem, a position which is strongly protected by neomycin B from Fe-OH. cleavage and which has been proposed to be involved in binding an essential metal ion, renders splicing resistant to neomycin. These results allowed the docking of neomycin to the core of the group I intron in the 3D model.

Anti-Bacterial Agents↗
PubMed2005

Contact allergy to neomycin sulfate: results of a multifactorial analysis.

PURPOSE: To perform a comprehensive, multifactorial analysis of potential risk factors (demographic and clinical) for contact allergy to neomycin sulfate, a common adverse reaction resulting from the topical use of this drug; especially in some subgroups of the population. METHODS: Retrospective analysis of allergy test data of the Information Network of Departments of Dermatology (IVDK, www.ivdk.org) between 1998 and 2003, including all patients patch tested with a standard screening series because of suspected allergic contact dermatitis (ACD). As one outcome, a positive (allergic) test reaction to neomycin sulfate was considered. An alternative outcome included only those patients with a positive test to neomycin sulfate and a final diagnosis of ACD. The association between outcome and potential risk factors was analyzed with Poisson regression analysis, deriving prevalence ratios (PR) as risk estimates. RESULTS: Of the 47,559 patients tested, 2.5% had positive reactions to neomycin sulfate, while in 1.1% ACD was additionally diagnosed. The results of the multifactorial analysis indicated that the risk of both outcomes decreased slightly during the period covered; was higher among patients with leg dermatitis; varied significantly with age and increased progressively with the number of additional positive reactions to other standard series allergens. Cross-reactivity to other, selectively tested, aminoglycoside antibiotics was substantial (kappa = 0.67; 95%CI: 0.63-0.71) for framycetin sulfate, to low (kappa = 0.33; 95%CI: 0.27-0.37) for gentamicin sulfate. CONCLUSIONS: The prevalence of contact sensitization to neomycin sulfate was noteworthy among patients patch tested in the IVDK centers. Supplementing clinical epidemiology, neomycin contact allergy has been estimated to be relatively common even on the level of the unselected population (prevalence approx. 1%). Hence, the topical use of neomycin sulfate by patients should be carefully monitored, considering its potential to induce ACD, with emphasis on subgroups at risk.

Administration, Topical↗
PubMed1994

Neomycin inhibits glycoprotein C (gC)-dependent binding of herpes simplex virus type 1 to cells and also inhibits postbinding events in entry.

Previous studies have identified requirements for the binding of herpes simplex virus type 1 (HSV-1) to cells, including the presence of particular glycoproteins in the virion envelope (gC or gB) and the presence of particular glycosaminoglycan chains (principally heparan sulfate) on cell surface proteoglycans. We show here that neomycin, a known inhibitor of HSV infection, blocked early events in HSV infection by two mechanisms: partial inhibition of the gC-dependent binding of virions, but not the gB-dependent binding, and inhibition of events that occurred after the binding of virus to cells. Near-maximal (but incomplete) inhibition of virus binding occurred at low concentrations of neomycin (1 mM) for wild-type and gB-negative virions only. Neomycin also inhibited the binding of isolated gC to cells at a similar concentration. Concentrations of neomycin as high as 50 mM had little or no effect on the binding of gC-negative virions to cells. Nevertheless, neomycin significantly inhibited infection by both wild-type and gC-negative virions, at concentrations greater than 10 mM, indicating that the inhibition at higher doses was not due to effects on virus binding. The effects of neomycin on virus binding suggest that gC (but not gB) and neomycin compete for binding to similar structural features of cell surface heparan sulfate.

Animals↗
PubMed1994

Neomycin reduces the intestinal production of ammonia from glutamine.

The mechanism by which neomycin treatment reduces circulating ammonia concentrations was studied in normal and portacaval shunted rats. Rats were given neomycin for 3 days and then fasted for 24 hours to eliminate feces. Neomycin decreased arteriovenous differences of ammonia across the intestine even when the intestines were empty. Neomycin treatment lowered the activity of glutaminase in the intestinal mucosa and the rate of ammonia production from glutamine by isolated intestinal segments. The intestines from portacaval shunted rats had higher glutaminase activity (by 57%), and produced ammonia from glutamine at a greater rate (by 31%), than intestines from controls. Neomycin treatment lowered glutaminase activity and ammonia production in shunted rats, but glutaminase activity still remained higher than in controls (by 23%). The data indicate that the mechanism by which neomycin lower plasma ammonia is owing, at least in part, to a direct effect on the intestines. Specifically, neomycin causes a reduction in mucosal glutaminase activity and thereby decreases the ability of the mucosa to consume glutamine and produce ammonia.

Ammonia↗
PubMed1993

Freeze fracture analysis of apical membranes in cochlear cultures: differences between basal and apical-coil outer hair cells and effects of neomycin.

Previous studies have shown that exposure of cochlear cultures to the ototoxic aminoglycoside antibiotic neomycin leads to the rapid formation of numerous membrane filled protrusions on the apical surface of the hair cells but not on the surrounding supporting cells, and that hair cells in basal-coil cultures are more sensitive to these effects of neomycin than those in the distal end of apical-coil cultures. Freeze-fracture has been used to examine and compare the apical surfaces of hair cells and supporting cells in basal and apical-coil cultures in order to look for features that may explain the differential sensitivity of the various cell types to neomycin, and to characterize the membrane type that forms in response to neomycin and compare it with the normal apical membrane of the hair cell. The apical surface of the highly responsive basal-coil outer hair cells differs significantly from the apical surfaces of apical-coil outer hair cells and supporting cells in both regions of the cochlea in both surface area and the number and density of endocytotic vesicles associated with this surface. Basal-coil hair cells have an average of 120 +/- 39 vesicles per cell surface and a density of 3.5 +/- 0.89 vesicles per microns 2, whereas apical-coil hair cells have 14.8 +/- 15.8 vesicles/cell surface and density of 0.73 +/- 0.72 vesicles per microns 2. There are no significant differences in intramembrane particle (IMP) density on the apical surfaces of all the cell types examined, and qualitative observations of filipin-treated specimens indicate that cholesterol densities are also similar. The membrane that accumulates in response to neomycin treatment at the apical pole of the hair cell is IMP free, does not respond to filipin, and fractures in a manner that is indicative of a high content of unsaturated phospholipid in a fluid phase, and is therefore different in several respects from the normal apical surface of the hair cell. The results of this study suggest that apical surface associated endocytotic vesicle numbers may determine the differential sensitivity of apical and basal-coil hair cells to neomycin, and that neomycin may interfere with some aspect of phospholipid metabolism or membrane turnover in sensory hair cells.

Animals↗
PubMed2000

Actions of neomycin on electrical light responses, Ca2+ release, and intracellular Ca2+ changes in photoreceptors of the honeybee drone.

Neomycin, known to inhibit phospholipase C-mediated IP3 formation, was applied in the bath or injected into cells and its effects on electrical light responses were analyzed. Neomycin effects on inositol 1,4,5-trisphosphate- and Ca2+-induced Ca2+ release from the endoplasmic reticulum and/or the light-induced Ca2+ elevation were also studied. Neomycin (0.5 mmol x l(-1)) blocked inositol 1,4,5-trisphosphate-, caffeine-, and Ca2+-induced Ca2+ release. Bath application of neomycin decreased the sensitivity to 20-ms light flashes by a factor of up to 100 and slowed the kinetics of dim flash responses. Intracellularly injected neomycin desensitized the photoreceptors more than 1 log unit, increased the latency, and slowed the rate of rise of the light response. Neomycin (0.5 mmol x l(-1)) in the bath delayed and reduced the transient component of responses to 1-s steps of light at intermediate intensities. It also decreased and slowed the light-induced, and it blocked the caffeine-induced intracellular Ca2+ elevation. The combined pharmacological effects of neomycin are suggested to decrease the Ca2+-mediated amplification of the phototransduction cascade and the Ca2+-mediated acceleration of processes determining the kinetics of light responses.

Adenosine Triphosphate↗
PubMed2003

Neomycin-induced hair cell death and rapid regeneration in the lateral line of zebrafish (Danio rerio).

Mechanoreceptive hair cells are extremely sensitive to aminoglycoside antibiotics, including neomycin. Hair cell survival was assessed in larval wild-type zebrafish lateral line neuromasts 4 h after initial exposure to a range of neomycin concentrations for 1 h. Each of the lateral line neuromasts was scored in live fish for the presence or absence of hair cells using the fluorescent vital dye DASPEI to selectively label hair cells. All neuromasts were devoid of DASPEI-labeled hair cells 4 h after 500 microM neomycin exposure. Vital DASPEI staining was proportional to the number of hair cells per neuromast identified in fixed larvae using immunocytochemistry for acetylated tubulin and phalloidin labeling. The time course of hair cell regeneration in the lateral line neuromasts was also analyzed following neomycin-induced damage. Regenerated hair cells were first observed using live DASPEI staining 12 and 24 h following neomycin treatment. The potential role of proliferation in regenerating hair cells was analyzed. A 1 h pulse-fix protocol using bromodeoxyuridine (BrdU) incorporation was used to identify S-phase cells in neuromasts. BrdU incorporation in neomycin-damaged neuromasts did not differ from control neuromasts 4 h after drug exposure but was dramatically upregulated after 12 h. The proliferative cells identified during a 1 h period at 12 h after neomycin treatment were able to give rise to new hair cells by 24-48 h after drug treatment. The results presented here provide a standardized preparation for studying and identifying genes that influence vertebrate hair cell death, survival, and regeneration following ototoxic insults.

Acetylation↗
PubMed1996

Neomycin inhibits histamine and thapsigargin mediated Ca2+ entry in DDT1 MF-2 cells independent of phospholipase C activation.

The histamine H1 receptor mediated increase in cytoplasmic Ca2+ ([Ca2+]i) was measured in the presence of the known phospholipase C (PLC) inhibitor, neomycin. Neomycin (1 mM) inhibited the histamine (100 microM) induced rise in [Ca2+]i to the same extent as observed after blocking Ca2+ entry with LaCl3. Likewise, the increase in [Ca2+]i after re-addition of CaCl2 (2 mM) to extracellular Ca2+ deprived and histamine pretreated cells was strongly reduced by neomycin. However, neomycin did not inhibit the histamine induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or the release of Ca2+ from internal stores. These results show that neomycin blocks histamine induced Ca2+ entry independent of phospholipase C activation. Inhibition of intracellular store Ca(2+)-ATPase by thapsigargin (1 microM), elicited an increase in [Ca2+]i due to a leakage from the stores, subsequently followed by store-dependent Ca2+ entry. Thapsigargin induced Ca2+ entry was also completely blocked by neomycin. These results indicate that neomycin inhibits histamine and thapsigargin induced Ca2+ entry. This inhibition is most likely exerted at the level of plasma membrane Ca2+ channels.

Animals↗
PubMed1993

Effect of neomycin on the hydrolysis and toxicity of vicine and convicine in rats.

This study in the rat established the effects that a broad-spectrum and poorly absorbed antibiotic, neomycin sulfate, had on the in vitro and in vivo hydrolysis of vicine and convicine by the intestinal microflora, and on vicine- and convicine-induced depletion of blood glutathione and the resulting toxicity. The in vitro studies demonstrated that digesta from the caecum and large intestine were highly effective in hydrolysing vicine and convicine, whereas digesta from the same sections of the gastro-intestinal tract of neomycin-treated rats were much less effective (P < 0.0001). The in vivo studies showed that the total amount of vicine and convicine excreted in the urine and faeces was much greater in neomycin-treated rats compared with controls (P < 0.05), indicating the ability of neomycin to increase the amount of glycosides, particularly that of vicine, excreted in the faeces. The ability of glycosides to decrease the concentration of glutathione in blood (P < 0.05) and to increase rat mortality was greatly reduced in rats that were treated with neomycin, particularly in those treated ip with the toxin. Thus, the results demonstrated that neomycin reduced the rate at which vicine and convicine were hydrolysed in the lower section of the gastro-intestinal tract, and that neomycin treatment was associated with a reduced toxicity of the glycosides.

Administration, Oral↗
PubMed2005

Development of ELISA and immunochromatographic assay for the detection of neomycin.

BACKGROUND: Reliable analytical methods are required to monitor neomycin residue levels in the livestock products. In particular, a more simple and rapid detection method is required in the veterinary fields. METHODS: Competitive direct ELISA and immunochromatographic assay were developed using monoclonal antibody to detect neomycin in the animal plasma and milk. RESULTS: No cross-reactivity of the antibody was observed with other aminoglycosides based on competitive direct ELISA methods, indicating that the antibody is highly specific for neomycin. Based on the standard curves, the detection limits were determined to be 6.85 ng/ml in PBS, 3.61 ng/ml in plasma, and 2.73 ng/ml in milk, respectively. Recoveries of neomycin from spiked plasma and milk at levels of 50-200 ng/ml ranged from 87% to 108%. Concentration of intramuscularly injected neomycin was successfully monitored in the rabbit plasma through competitive direct ELISA. Immunochromatographic method was also developed using colloidal gold-conjugated monoclonal antibody. Through this method, the detection limits were estimated to be about 10 ng/ml of neomycin in PBS, plasma, and milk. CONCLUSIONS: Immunochromatographic assay developed in this study is suitable for the simple screening of neomycin residues in the veterinary field. Observed positives can be confirmed using a more sensitive laboratory method such as competitive direct ELISA.

Animals↗
PubMed2006

Determination of neomycin sulfate and impurities using high-performance anion-exchange chromatography with integrated pulsed amperometric detection.

Neomycin B is one of a class of aminoglycoside antibiotics that lack a good chromophore, and is therefore difficult to determine using reversed-phase HPLC with absorbance detection. This is especially true for determining the quantity of each impurity. We show that neomycin sulfate and its major impurities, including neamine (neomycin A), can be separated on a strong anion-exchange column using a weak potassium hydroxide eluent (2.40 mM) at a column temperature of 30 degrees C, and directly detected by integrated pulsed amperometric detection (IPAD). The resolution (United States Pharmacopeia (USP) definition) between neomycin B and the closest major impurity ranged from 6.56 and 7.45 over 10 days of consecutive analysis (7.24+/-0.10, n=836 injections). Due to the difficulty of producing weak hydroxide eluents of the required purity (i.e. carbonate-free), this method depends on automatic eluent generation to ensure method ruggedness. This method exhibited good long-term (10 days, 822 injections) retention time stability with a R.S.D. of 0.6%. Peak area R.S.D. (10 microM) was 1.3%. Method robustness was evaluated by intentionally varying the flow rate, eluent concentration, column temperature, and column. The spike recoveries of neomycin B from extractions of three different topical ointments and cream formulations ranged from 95 to 100%. The measured concentration of neomycin B in these formulations ranged from 119 to 154% of the label concentration. The R.S.D. for the measured concentration of one of the formulations tested over three separate days, n=11 extracts, was 3.2%. Based on the results of these evaluations, we believe this method can be used for neomycin sulfate identity, assay, and purity.

Aminoglycosides↗
PubMed2002

Effects of neomycin on high-threshold Ca(2+) currents and tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion neuron.

High-threshold Ca(2+) channels and tetrodotoxin-resistant Na(+) channels are highly expressed in small dorsal root ganglion neurons. In acutely isolated rat dorsal root ganglion neurons, the effects of neomycin, one of the aminoglycoside antibiotics, on high-threshold Ca(2+) currents and tetrodotoxin-resistant Na(+) currents were examined using whole-cell patch recording. We showed for the first time that neomycin dose-dependently inhibited peak high-threshold Ca(2+) currents and peak tetrodotoxin-resistant Na(+) currents with half-maximal inhibitory concentrations at 3.69 microM (n=20) and 1213.44 microM (n=25), respectively. Inactivation properties of high-threshold Ca(2+) currents and activation properties of tetrodotoxin-resistant Na(+) currents were also affected by neomycin with reduction of excitability of small dorsal root ganglion neurons. Half-maximal inactivation voltage of high-threshold Ca(2+) currents was -45.56 mV before and -50.46 mV after application of neomycin (n=10). Half-maximal activation voltage of tetrodotoxin-resistant Na(+) currents was -19.93 mV before and -11.19 mV after administration of neomycin (n=15). These results suggest that neomycin can inhibit high-threshold Ca(2+) currents and tetrodotoxin-resistant Na(+) currents in small dorsal root ganglion neurons, which may contribute to neomycin-induced peripheral and central analgesia.

Animals↗