Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Benzocaine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

Rates of block by procaine and benzocaine and the procaine-benzocaine interaction at the node of Ranvier.

1. Action potentials and their maximum rates of rise, VA, were measured in single myelinated nerve fibres of the frog, Rana esculenta at room temperature. 2. On applying 1 mM procaine (pH 7.2) at 20 Hz stimulus frequency, half of the final VA reduction was reached at ton = 0.27 s; on applying 0.5 mM benzocaine (pH 7,2) at 50 HZ, ton was 0.12 s. Increasing the stimulus frequency between 2 and 50 HZ increased the rate of block by procaine but not by benzocaine. 3. Recovery in Ringer solution (pH 7.2) from 30-s treatment with 1 mM procaine (pH 7.2), the equieffective 0.15 mM procaine (pH 8.9) and from 0.5 mM benzocaine (pH 7.2) was 54%, 31% and 70%, respectively, within 1 s. 4. Changing between alkaline Ringer solution (pH 8.9) and 1 mM procaine (pH 7.2) led to transitory excessive block. Changing between 1 mM procaine (pH 7.2) and acid Ringer solution (pH 6.0) and washing out 10 mM procaine (pH 5.5) with neutral Ringer solution also led to a non-monotonic change in VA. 5. If hyperpolarizing pulses (30 ms, 20 mV) preceded the stimuli, changing the frequency of the pulse pairs led to a gradual moderate relief of block in procaine, turning off prepulses (at 10 HZ) to a gradual increase of block. In benzocaine changing from 1 to 10 HZ had no effect but turning off prepulses led to a prompt large increase of block. In procaine + benzocaine the membrane responded much as in benzocaine alone. At 1 HZ (prepulses) VA in 0.4 mM procaine was smaller than in 0.4 mM procaine + 0.3 mM benzocaine. 6. These phenomena can be explained on the assumption of voltage-dependent binding of benzocaine and procaine to a common receptor. The rate of block appears to be limited by access to the receptor, more in the case of benzocaine than of procaine.

Action Potentials↗
PubMed2000

Effects of temperature on the elimination of benzocaine and acetylated benzocaine residues from the edible fillet of rainbow trout (Oncorhynchus mykiss).

The effect of temperature (7 degrees C and 16 degrees C) on the extent of accumulation and the elimination of benzocaine (BNZ) and its metabolite, acetylated benzocaine (AcBNZ), in the fillet tissue of rainbow trout was investigated. Residues were measured after bath exposure to an anesthetizing concentration of benzocaine (30 mg/l for 5 min) followed by a maintenance concentration (15 mg/l for 30 min). Immediately after exposure, the BNZ concentration in fillet tissue was approximately 27 micrograms/g at both temperatures; AcBNZ was 0.3 microgram/g at 7 degrees C and 0.6 microgram/g at 16 degrees C. The rates for elimination (alpha and beta) of BNZ and AcBNZ were not significantly different between the two temperatures. Terminal half-lives of elimination for BNZ were 1.62 h at 7 degrees C and 1.63 h at 16 degrees C; half-lives for AcBNZ were 2.36 h at 7 degrees C and 2.77 h at 16 degrees C.

Anesthetics, Local↗
PubMed1992

Topical anesthetic-induced methemoglobinemia in sheep: a comparison of benzocaine and lidocaine.

Benzocaine induces methemoglobin (MHb) in several species, whereas lidocaine may increase MHb in cats and human. Elevated MHb (greater than 20%) in sheep after benzocaine exposure was recently recognized. MHb decreases blood oxygen-carrying capacity which can complicate interpretation of experimental data. Sheep are used in research which requires tracheal intubation and blood gas analysis. Since benzocaine and lidocaine are used to provide local anesthesia prior to intubation, we compared MHb production by sheep after exposure to these drugs. A dose-response relationship between benzocaine and MHb was investigated. Eight crossbred Dorset ewes were dosed intranasally with benzocaine for 2 sec or with 40 mg of lidocaine in a randomized crossover design. Sheep with elevated MHb after the 2-sec benzocaine dose were later dosed with benzocaine intranasally for 10 sec. MHb levels were measured periodically on a CO-Oximeter. A quantitative MHb response to an indirect MHb former, p-aminopropiophenone (PAPP), by each sheep was determined 15 min after PAPP (0.6 mg/kg iv). MHb levels remained at baseline (1-2%) after lidocaine exposure in all sheep, as well as in four sheep (nonresponders) after the 2-sec benzocaine dose. Four sheep (responders) demonstrated 16.5-26.4% MHb after the 2-sec benzocaine dose. The responders formed 38.2-50.5% MHb after the 10-sec benzocaine dose. All responders developed high MHb after PAPP, while nonresponders developed slightly elevated MHb after PAPP. An N-hydroxy metabolite of benzocaine is the likely active MHb-forming substance. Benzocaine should be replaced by lidocaine when local anesthesia of the nasal or oropharyngeal region in sheep is required.

Administration, Topical↗
PubMed2002

Putative binding sites for benzocaine on a human cardiac cloned channel (Kv1.5).

OBJECTIVES: It has been demonstrated that at nanomolar concentrations benzocaine increased, whereas at micromolar concentrations, it blocked hKv1.5 channels in a voltage-dependent manner and modified the voltage-dependence of channel activation. The present study was undertaken to localize the putative binding sites involved in the 'agonists' and blocking effects of benzocaine. METHODS: Experiments were carried out on wild-type and site directed mutated hKv1.5 channels stably expressed on Ltk(-) cells using the whole-cell patch-clamp. RESULTS: At 35 mM [K+](i) the voltage-dependent unblock produced by 500 microM benzocaine was preserved at both 4 and 140 mM [K+](o). Mutations located in the inner mouth of the pore (T477S, T505A, L508M and V512M) abolished the agonist but increased the blocking effects of benzocaine. Intracellular application of tetraethylammonium (3 mM) abolished the 'agonist' effects whereas the blocking effects of benzocaine remained unaltered. Block induced by benzocaine and intracellular tetraethylammonium was additive. In contrast, the combination of benzocaine and bupivacaine (>25 microM) produced less blockade than bupivacaine alone. However, mutation of the extracellular residue R485Y did not modify the effects of benzocaine. Extracellular application of tetraethylammonium (100 mM) did not modify the agonist effects of benzocaine, but abolished the voltage- and time-dependence of benzocaine-induced block. CONCLUSIONS: The results suggested that benzocaine binds with high affinity to an intracellular binding site to produce 'agonist' effects and to a low affinity subsite, which is also located in the inner mouth, to produce the blocking effects. Furthermore, benzocaine and extracellular K(+) interact to modify the voltage-dependence of channel opening.

Animals↗
PubMed1991

Metabolism and elimination of benzocaine by rainbow trout, Oncorhynchus mykiss.

1. Branchial and urinary elimination of benzocaine residues was evaluated in adult rainbow trout, Oncorhynchus mykiss, given a single dorsal aortic dose of 14C-benzocaine hydrochloride. 2. Branchial elimination of benzocaine residues was rapid and accounted for 59.2% of the dose during the first 3 h after dosing. Renal elimination of radioactivity was considerably slower; the kidney excreted 2.7% dose within 3 h and 9.0% within 24 h. Gallbladder bile contained 2.0% dose 24 h after injection. 3. Of the radioactivity in radiochromatograms from water taken 3 min after injection, 87.3% was benzocaine and 12.7% was N-acetylated benzocaine. After 60 min, 32.7% was benzocaine and 67.3% was N-acetylated benzocaine. 4. Of the radioactivity in radiochromatograms from urine taken 1 h after dosing, 7.6% was para-aminobenzoic acid, 59.7% was N-acetylated para-aminobenzoic acid, 19.5% was benzocaine, and 8.0% was N-acetylated benzocaine. The proportion of the radioactivity in urine changed with time so that by 20 h, 1.0% was para-aminobenzoic acid and 96.6% was N-acetylated para-aminobenzoic acid. 5. Benzocaine and a more hydrophobic metabolite, N-acetylated benzocaine, were eliminated primarily through the gills; renal and biliary pathways were less significant elimination routes for benzocaine residues.

Animals↗
PubMed1980

Interaction of lidocaine and benzocaine in blocking sodium channels.

1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated in voltage and current clamp experiments at pH 7.2 2. Measured with infrequent test pulses, 0.123 mM lidocaine reduced INa to 54%, 0.25 mM benzocaine to 40% and the mixture 0.125 mM lidocaine +/- 0.25 mM benzocaine to 31% of the control. When hyperpolarizing prepulses (V = -40 mV for 15 ms) preceded the test pulses the respective reductions were to 58%, 74% and 55% i.e. adding benzocaine to lidocaine had little additional effect. 3. Increasing the rate of the prepulse-test pulse pairs from 1 to 20 Hz did not change INa in benzocaine but gradually relieved block by lidocaine; in the mixture this change was much reduced or absent. 4. Switching off prepulses (at 20 Hz) led to a gradual decrease of INa in lidocaine but to a prompt fall in benzocaine and in the mixture. 5. 0.25 mM lidocaine and 0.5 mM benzocaine were approximately equieffective in reducing INa (no prepulse) to 29% and 24%; a one-to-one mixture of the two solutions (0.125 mM lidocaine + 0.25 mM benzocaine) reduced to 27%. 6. In current clamp experiments 0.25 mM lidocaine and 0.36 mM benzocaine reduced the maximum rate of rise of the action potential to 32% and 30%, the mixture of solutions (0.125 mM lidocaine + 0.18 mM benzocaine) to 29%. 7. These results are fully compatible with the idea of a single common binding site for which lidocaine and benzocaine compete.

Animals↗
PubMed1999

A 10-year retrospective study on benzocaine allergy in the United Kingdom.

BACKGROUND: Benzocaine has been labeled a notorious sensitizer. It is thought to be a common and potent sensitizer. It is suggested that such patients should routinely avoid tetracaine and procaine, as cross-reactions between benzocaine and such caines occurred commonly. Benzocaine also currently remains the screening chemical on the European Standard Battery (ESB) for topical caine allergy. OBJECTIVE: To identify the rate of incidence of benzocaine allergy in the United Kingdom, and the level of cross reactivity between other caines in the ESB. METHODS: The results from a 10-year retrospective study of 5,464 patients, subjected to patch testing with a modified ESB, which included caine mix III (Chemotechnique Diagnostics, Tygelsjo, Sweden), and the results of caine mix IV (Chemotechnique) reactions in 265 of these patients who complained of anogenital symptoms, are discussed. RESULTS: Majority of allergic reactions occurred with the constituents of caine mix III, with benzocaine reactions being the least common allergen in this group. Cross reactivity between benzocaine and other caines, occurred infrequently. CONCLUSION: Our data indicate that benzocaine allergy is not common in the United Kingdom. As cross-reactivity between benzocaine and other caines did not occur commonly, a significant number of relevant allergic reactions to other caines may go undetected, as benzocaine remains the screening chemical for topical anaesthetic allergy on the ESB. We suggest benzocaine be removed from the ESB, and be replaced by caine mix III.

Anesthetics, Local↗
PubMed1994

Binding of benzocaine in batrachotoxin-modified Na+ channels. State-dependent interactions.

Hille (1977. Journal of General Physiology. 69:497-515) first proposed a modulated receptor hypothesis (MRH) to explain the action of benzocaine in voltage-gated Na+ channels. Using the MRH as a framework, we examined benzocaine binding in batrachotoxin (BTX)-modified Na+ channels under voltage-clamp conditions using either step or ramp command signals. We found that benzocaine binding is strongly voltage dependent. At -70 mV, the concentration of benzocaine that inhibits 50% of BTX-modified Na+ currents in GH3 cells (IC50) is 0.2 mM, whereas at +50 mV, the IC50 is 1.3 mM. Dose-response curves indicate that only one molecule of benzocaine is required to bind with one BTX-modified Na+ channel at -70 mV, whereas approximately two molecules are needed at +50 mV. Upon treatment with the inactivation modifier chloramine-T, the binding affinity of benzocaine is reduced significantly at -70 mV, probably as a result of the removal of the inactivated state of BTX-modified Na+ channels. The same treatment, however, enhances the binding affinity of cocaine near this voltage. External Na+ ions appear to have little effect on benzocaine binding, although they do affect cocaine binding. We conclude that two mechanisms underlie the action of local anesthetics in BTX-modified Na+ channels. Unlike open-channel blockers such as cocaine and bupivacaine, neutral benzocaine binds preferentially with BTX-modified Na+ channels in a closed state. Furthermore, benzocaine can be modified chemically so that it behaves like an open-channel blocker. This compound also elicits a use-dependent block in unmodified Na+ channels after repetitive depolarizations, whereas benzocaine does not. The implications of these findings for the MRH theory will be discussed.

Animals↗
PubMed2005

A study of benzocaine gel dosing for toothache.

OBJECTIVE: This pilot study evaluated subject compliance with a proposed OTC label with improved dosing directions for self-application of a 20% benzocaine gel for toothache pain, and assessed the methodology for evaluating efficacy in a future pivotal study of benzocaine gel. It was hypothesized that > or = 75% of subjects would apply < or = 400 mg of product (80 mg benzocaine). Exploratory analyses of efficacy were also performed. METHODOLOGY: Thirty patients with spontaneous pain of moderate or severe intensity from a single tooth due to caries, a lost restoration, or a fracture entered this randomized, parallel group, double-blind study. Before self-applying 20% benzocaine gel or placebo, patients read a label containing new dosing directions, including a picture of how much product to apply to their tooth and the surrounding gingival tissues. The amount applied was determined by weighing the tube before and after dosing. Following dosing, pain intensity and relief were recorded every five minutes through 30 minutes, then every ten minutes through 120 minutes. Responders were defined as those subjects who experienced at least a one-unit reduction in pain intensity from baseline at two consecutive time points within the first 20 minutes. Onset of meaningful relief was recorded using a stopwatch. The percentage of responders was compared using the Mantel-Haenszel test. ANOVA was employed to test for differences in Pain Relief Combined with Pain Intensity Difference (PRID), and the areas under the curve at 30, 60, 90, and 120 minutes for this measure (SPRID). Median onset and duration times were compared using the Cox proportional hazards model. Adverse events were recorded if and when they occurred. RESULTS: It was found that 86.7% of the subjects (26/30) applied < or = 375 mg of product (mean +/- SD = 327.7 +/- 276.8 mg). The benzocaine group had a significantly higher (p = 0.022) responder rate (86.7%) than the placebo group (46.7%). Significant differences in favor of the benzocaine group were also recorded for PRID at 10, 15, and 30 minutes (p < 0.05) and SPRID-30 (p = 0.037). Median onset and duration times were 8.3 minutes and > 115 minutes for the benzocaine group, >120 minutes and 5 minutes for the placebo group. There were no adverse events recorded in the study. CONCLUSION: The improved dosing directions resulted in a high percentage of subjects self-applying an appropriate amount of benzocaine gel or matching placebo. The label and study methodology appear suitable for a pivotal dose-response study in subjects with toothache pain. While the current study was not statistically powered to make firm efficacy conclusions, 20% benzocaine gel appeared more efficacious than placebo, providing a rapid onset of pain relief and a relatively long duration of action.

Adolescent↗
PubMed1981

Block of Na channels in the membrane of myelinated nerve by benzocaine.

The actions of the neutral local anesthetic benzocaine on Na channels were studied in voltage-clamp experiments on single myelinated nerve fibres of the frog by measurements of sodium currents, asymmetry currents, and sodium current fluctuations. 2. 1 mM benzocaine reduced the peak Na currents during various depolarizations V between 20 and 120 nV to 63% of their control values but did not change the time constant of Na activation. 3. 1 mM benzocaine altered asymmetry currents during 1 ms pulses V between 20 and 120 mV in the same was as the early Na currents: It reduced the amplitude to 64% but did not affect the kinetics of the currents. 4. The charge displacement of the asymmetry current during the pulse (Qon) was compared with the charge displacement after the pulse (Qoff). Without benzocaine the relative charge Qoff/Qon Declined to a constant level (0.42 at V = 40mV, 0.25 at V = 100 mV) with increasing pulse durations. In the presence of 1 mM benzocaine the charges Qoff after pulses to V = 40 or 100 mV are almost independent of pulse duration and approximately equal to the control Qoff values after 5.6 ms pulses. Thus, the immobilizations caused by Na inactivation and benzocaine are not additive. 5. Na currents and Na-current fluctuations were recorded during depolarizations V between 24 and 48 mV in the presence of 0.1 mM benzocaine and 7 microM Anemonia toxin II. A lower limit of 8.6 pS was derived for the conductance of a single Na channel. The value agrees with other estimates of the conductance of Na channels which had not been treated by local anesthetics. This suggests an "all-or-none blocking" of Na channels by benzocaine.

Animals↗
PubMed2001

Canister tip orientation and residual volume have significant impact on the dose of benzocaine delivered by Hurricaine spray.

Delivered quantities of 20% benzocaine spray (Hurricaine; Beutlich L.P. Pharmaceuticals, Waukegan, IL) are estimated by counting the number of sprays or the spraying time. Because Hurricaine spray supplies a continuous (albeit nonmetered) stream of benzocaine, neither method addresses delivered dose. We hypothesized that dose per time is a function of canister content and orientation. Thirty full canisters of Hurricaine were placed into three equal orientations (upright, inverted, or horizontal). Extrapolating from a full canister, four different estimates of benzocaine residual volume were determined before spraying out the contents (80%, 60%, 40%, and 20% full). Each canister was then sprayed for 10-s intervals, and the quantity delivered was calculated and compared statistically. Upright canisters 100% full emitted more benzocaine than canisters with residual volume 20% full (190 +/- 10 vs 172 +/- 10 mg/s). Inverted canisters emitted significantly less benzocaine from 100% full to residual volume 20% full (188 +/- 14 vs 70 +/- 10 mg/s). Oriented horizontally, two full canisters emitted <76 mg/s benzocaine, contrasted with the remaining eight in that group (186 +/- 20 mg/s). We conclude that the benzocaine (Hurricaine) sprayed in milligrams per second depends on canister content and orientation. When residual volumes diminish, there is a reduction in spraying volume per time. This diminution occurs progressively from larger to smaller residual volumes with canisters oriented horizontally, inverted, or upright. Arbitrary documentation of spraying time bears no relationship to dose delivered. Perhaps affixing an atomization device to a graduated syringe filled with benzocaine will help increase accuracy and precision in dosing.

Anesthesia, Local↗
PubMed2005

Death of an infant involving benzocaine.

This report describes the death of a four-month-old Hispanic male which may be related to benzocaine toxicity. A toxicological evaluation revealed benzocaine at a concentration of 3.48 mg/L, and postmortem methemoglobin of 36% (normal 0.4-1.5). Methemoglobinemia is a complication of benzocaine toxicity. In light of the toxicology findings, the coroner investigated the source of the benzocaine and discovered that the child was treated with Zenith Goldline Allergen Ear Drops containing 0.25% w/v benzocaine and 5.4% w/v antipyrine. There was an admission by a caregiver that on the day prior to the child's death, he had been treated with three times the prescribed dose. Blood benzocaine concentrations in nine other unrelated cases were determined and concentrations ranged from <0.05-5.3 mg/L (mean 1.48 mg/L). Seven of the nine cases were positive for drugs of abuse, and one additional case was described as a known drug user. Methemoglobin in these benzocaine positive cases ranged from 6-69%; however, methemoglobin concentrations in postmortem cases are frequently elevated and should be interpreted with caution. The unknown significance of the benzocaine, and the circumstances of the case raise questions about the ultimate attribution of this death to SIDS.

Anesthetics, Local↗
PubMed1987

The mechanisms of sodium current inhibition by benzocaine in the squid giant axon.

(1) The effects of benzocaine on the ionic currents in the voltage-clamped squid giant axon have been examined under various conditions; intact axons, axons internally perfused with CsF and axons dialysed with tetraethylammonium ions were used. (2) Both the steady state outward (potassium) current and the early transient (sodium) current were reduced by ca. 50% by benzocaine (1 mM). (3) Plots of the changes produced by benzocaine (1 mM) in the Hodgkin-Huxley parameters for the steady state activation (m infinity), the steady state inactivation (h infinity) and the time constants (tau m and tau h) for activation and inactivation of the sodium current are shown. The m infinity and h infinity curves are shifted in positive and negative directions respectively on the voltage axis. The time constants are not greatly affected. (4) In axons in which the sodium current inactivation had been largely removed by treatment with chloramine T, the sodium current was still reduced by ca. 50% by 1 mM benzocaine and the positive shift in activation remained unchanged. (5) The dependence on benzocaine concentration (for less than or equal to 2 mM) of the peak sodium current reduction and the shift in steady state inactivation have been determined. (6) It is concluded that in the squid axon the effects on inactivation are not the main reason for the reduction of the sodium current by benzocaine and that, in common with many other neutral anaesthetics, there are at least two sites at which benzocaine acts.

Animals↗
PubMed1994

In vivo effects of the anesthetic, benzocaine, on liver microsomal cytochrome P450 and mixed-function oxidase activities of gilthead seabream (Sparus aurata).

Gilthead seabreams were exposed to benzocaine, 4-aminobenzoic acid ethyl ester, 57 mg/l in sea water for 3 min, daily, for 2 or 3 consecutive days. The fish were killed 20 hr after the last treatment. Benzocaine treatment for 2 or 3 days resulted in 57% and 67% inhibition of liver microsomal aniline 4-hydroxylase and ethylmorphine N-demethylase activities, respectively. The total cytochrome P450 content of fish liver microsomes was unaltered following the 2-day benzocaine treatment. However, additional 3 min benzocaine treatment on day 3 reduced cytochrome P450 level by 50%. Benzocaine produced type II difference spectra with rabbit liver microsomes. Difference spectra of fish liver microsomes elicited by benzocaine were complex. The position of peak and intensity were greatly influenced by the concentration of benzocaine.

Animals↗