Analgesic efficacy of articaine hydrochloride for velvet antler removal in red deer (Cervus elaphus) and analysis of drug residues in the harvested velvet antlers.

AIMS: To investigate the analgesic efficacy of articaine hydrochloride for antler removal in red deer (Cervus elaphus) following S/C administration as a ring block, and to quantify the residue concentrations of articaine compared to lignocaine in the harvested antlers. METHODS: Articaine hydrochloride (40 mg/mL) was administered to 10 male red deer as a ring block around the base of each antler at 1 mL/cm of pedicle circumference. Analgesia was evaluated by determining the response to a saw cut test every 1-minute, until no response was observed. Behaviour during and following removal of antlers was also recorded. Twenty commercially harvested velvet antlers were also collected following S/C administration of 2% lignocaine hydrochloride. A liquid chromatography-mass spectrometry (LC-MS) method for quantification of residues of articaine and lignocaine in velvet antlers was developed and validated. RESULTS: In red deer administered 4% articaine hydrochloride as a ring block, the median interval to analgesia was 4 (min 3, max 5) minutes and no deer showed withdrawal responses during antler removal. There were no signs of toxicity or adverse effects up to 2 hours after administration. The sample preparation method developed for the LC-MS was simple and had acceptable extraction recoveries of articaine and lignocaine from the velvet antlers. The lower limits of quantification of lignocaine and articaine were 5 and 50 ng/g, respectively. Mean concentrations of articaine in antlers following ring block with 4% articaine hydrochloride were 1.50 (SD 1.09) mg/kg, and of lignocaine following ring block with 2% lignocaine hydrochloride were 0.66 (SD 0.71) mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: A ring block with 4% articaine hydrochloride at a dose of 1 mL/cm of pedicle circumference provided effective analgesia for velvet antler removal in red deer. The LC-MS method developed and validated to quantify articaine and lignocaine was simple and sensitive. Based on these results, articaine hydrochloride appears to be an effective alternative to lignocaine hydrochloride for velvet antler removal. However, further studies to evaluate the safety and residue concentrations of articaine and articainic acid are required before it can be recommended for use in deer.Abbreviations: DMA: 2,6-dimethylaniline; LC-MS: Liquid chromatography-mass spectrometry; MEGX: Monoethylglycinexylidide; MRL: Maximum residue level.

Articaine Versus Lidocaine Concentration in the Palatal Tissues After Supraperiosteal Buccal Infiltration Anesthesia.

PURPOSE: Palatal local anesthetic injection is a painful procedure. Previous studies have reported successful extraction of maxillary teeth using only buccal infiltration of 4% articaine without palatal anesthesia. The aim of the present study was to determine levels of 4% articaine solution in palatal bone and mucosal tissues after buccal injection and compare those levels with 2% lidocaine solution in New Zealand white rabbits. MATERIALS AND METHODS: Eight rabbits received 2 different injections of 0.6 mL of 4% articaine with 1:100,000 epinephrine and 0.6 mL of 2% lidocaine with 1:100,000 epinephrine buccal to the right and left maxillary first molar, respectively, in a split-mouth study design using quantitative syringes. All injections were administered using the buccal infiltration technique without any palatal injection. Ten minutes later, palatal bone and mucosa specimens were collected for analysis. Levels of the 2 local anesthetic agents were measured in palatal tissues using high-performance liquid chromatography (HPLC). RESULTS: HPLC analysis showed markedly higher 4% articaine solution values (0.319 ± 0.037) in palatal mucosal tissues compared with palatal mucosal concentrations of 2% lidocaine solution (0.0839 ± 0.017). In palatal bone, the mean concentration of 2% lidocaine solution was markedly lower than the mean concentration of 4% articaine solution (0.085 ± 0.012 vs 0.155 ± 0.012, respectively). There was no relevant difference between levels of 2% lidocaine in the palatal bone and mucosal tissues. However, the mean concentration of 4% articaine in the palatal mucosa was markedly higher than its concentration in palatal bone. CONCLUSIONS: The buccal vestibule-palatal diffusion of 4% articaine solution with 1:100,000 epinephrine is greater than 2% lidocaine solution with 1:100,000 epinephrine in a rabbit model.

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus).

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle. METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis. RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10 ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.

Early Nonclinical and Clinical Development of AG-920, a Repurposed Topical Ocular Anesthetic.

Purpose: To evaluate the preclinical effects, and preclinical and clinical ocular and systemic pharmacokinetics of a new topical, non-preserved ocular anesthetic, AG-920 (articaine ophthalmic solution). Methods: Five studies: one in vitro melanin binding study; three studies in rabbits receiving an ocular dose of AG-920 evaluating corneal sensitivity, ocular tolerability, and systemic exposure to articaine and its inactive metabolite, articainic acid; and one clinical study in 14 healthy adult volunteers receiving an ocular dose of AG-920, with blood samples over 24 h. A liquid chromatography with tandem mass spectrometry (LC-MS-MS) method was used to detect both parent and metabolite with a lower limit of quantitation (LLOQ) of 0.1 and 0.2 ng/mL, respectively. Results: Melanin binding of articaine was up to 7.4%. A decrease in corneal sensitivity was noted for 20 min post-treatment in all active groups, and returned to baseline by 60 min post-dose. No dose-response relationship was observed. Concentrations of articaine in ocular matrices generally peaked early and then decreased over time. Both parent and metabolite were observed in blood at early time points. There were no ocular safety issues with AG-920. Conclusions: These early stage development studies showed that AG-920 was well tolerated in the standard preclinical models and did not cause any toxicity. AG-920 ophthalmic solution elicited a rapid onset and potentially clinically useful duration of corneal anesthesia. The studies supported the clinical evaluation of the 8% strength. Registered with clinicaltrials.gov as NCT04759339.

Distribution and absorption of local anesthetics in inferior alveolar nerve block: evaluation by magnetic resonance imaging.

PURPOSE: The aim of this study was to evaluate the distribution and absorption of local anesthetic solutions in inferior alveolar nerve block using magnetic resonance imaging. MATERIALS AND METHODS: Forty healthy volunteers were divided into 4 groups and injected with 1.5 mL for inferior alveolar nerve block and 0.3 mL for lingual nerve block. The solutions used for the different groups were 2% lidocaine, 2% lidocaine with 0.125 mg/mL epinephrine, 4% articaine with 0.006 mg/mL epinephrine, and 4% articaine with 0.012 mg/mL epinephrine. All subjects had axial T2-weighted and fat-suppressed images at 0, 60, and 120 minutes after injection. The localization, area, and intensity (signal characteristics) of the solutions were analyzed and onset and duration times of the anesthesia were recorded. RESULTS: There were no significant differences between groups with regard to the intensity and area of the solutions at 0, 60, and 120 minutes after injection, but differences were found within each group. CONCLUSIONS: No between-group differences were found on magnetic resonance imaging in the distribution and absorption of lidocaine with or without epinephrine and articaine with 0.006 and 0.012 mg/mL epinephrine. All solutions were noticeably absorbed at 120 minutes after injection.

[Effect of intraligamentary anesthesia with various preparations of articaine on arterial pressure and heart rate].

In 56 laboratory blind investigations in 26 volunteers effects of intraligamentary anesthesia with 4% articaine solutions with different adrenaline concentrations and without it on arterial pressure and heart rate changes by means of automatic monitor were evaluated. Period of intraligamentary injection of anesthetic solutions (1-2 min) was chacterized by the most manifestation of these reactions which might be due to vascular distribution of the anesthetic solution within tissues as well as adrenaline content in it.

A novel LC-MS/MS analytical method for detection of articaine and mepivacaine in blood and its application to a preliminary pharmacokinetic study.

Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitory inhibition of nerve signal due to the blockade of the voltage-gated sodium channels. LAs are administrated alone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurological and cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratory depression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for the simultaneous detection of articaine and mepivacaine in whole blood. Sample treatment consisted in a liquid-liquid extraction with phosphate buffer (pH 8, 0.1 M) and ethyl-acetate. Analysis was performed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode (transitions: articaine, 285→8658 m/z; mepivacaine, 247→9870 m/z; lidocaine - internal standard -, 235→8658 m/z). The method proved to be highly sensitive with limit of quantifications for articaine and mepivacaine of 0.8 and 0.1 ng/mL, respectively. Accuracy and precision were always within the acceptance criteria. The new procedure was also successfully applied to a preliminary pharmacokinetics study.

Evaluation of the buccal vestibule-palatal diffusion of 4% articaine hydrochloride in impacted maxillary third molar extractions.

AIMS: The aim of this study was to evaluate the vestibular-palatal diffusion of 4% Articaine with epinephrine 1:100,000 and 1:200,000, in impacted maxillary third molar extractions, without palatal injection. MATERIALS AND METHOD: Two hundred teeth were selected from patients age 15 to 46. Patients were divided into 4 groups: 1A, were anesthetized with 4% articaine 1:100,000 and the surgery was initiated 5 minutes following anesthesia. 1B, used 4% articaine 1:100,000 but the surgery was started 10 minutes after anesthesia. 2A, used 4% articaine 1:200,000 the surgery was started 5 minutes after. 2B, used 4% articaine 1:200,000 but 10 minutes was allowed for anesthetic diffusion before the initiation of in groups (50 extractions each) only buccal vestibule anesthesia was initially administered (i.e. no palatal injections were used). RESULTS: The rate of sufficient vestibule-palatal diffusion, as determined by the lack of necessity of supplemental palatal anesthesia, was: 1A(84%), 1B(98%), 2A(78%), 2B(82%). Chi-square (Chi2) and residual analyses showed that a higher vestibule-palatal diffusion was obtained using 4% articaine 1:100,000 with a period of 10 minutes (p<0.05). CONCLUSIONS: Most of the extractions could be performed only with vestibule anesthesia. However, vasoconstrictor concentration and the time interval between administration of the anesthetic and initiation of surgery did influence buccal vestibule-palatal diffusion of 4% articaine in the extraction models used.

Population pharmacokinetics of articaine with 1:200,000 epinephrine during third molar surgery and simulation of high-dose regimens.

BACKGROUND AND OBJECTIVES: Articaine is more and more used in third molar surgery under local anesthesia (LA). The objectives of this analysis were to characterize the pharmacokinetics of articaine for this type of surgery and to simulate dosing regimens. METHODS: Non-linear mixed-effects modeling conducted in Monolix 4.4.0 was used to describe articaine plasma concentration-time data from 20 patients. Monte Carlo simulations were then performed to evaluate the probability of cardiotoxic target attainment (PCTA) of various dosage regimens. RESULTS: Articaine concentration data were best described by a linear one-compartment model, with an additional depot compartment for submucosal route with a zero-order transfer to central compartment. Age and gender were found to influence duration transfer (Tk0) and elimination rate constant (Ke), respectively. Simulated maximum recommended dose regimen (7mg/kg) had a PCTA of 0%. Simulated higher doses of 10mg/kg and 15mg/kg had a PCTA of 0% and about 1-4%, respectively. CONCLUSIONS: The model adequately described the articaine pharmacokinetics. This is the first PK model qualified for articaine administered by submucosal route. The simulations suggest that maximum recommended dose regimen is safe concerning the cardiotoxicity in healthy patients.

The pharmacokinetics and cardiovascular effects of high-dose articaine with 1:100,000 and 1:200,000 epinephrine.

OBJECTIVES: The authors conducted a randomized, double-blind, two-way crossover clinical trial to compare the pharmacokinetics and cardiovascular effects of 11.9 milliliters of 4 percent articaine hydrochloride (HCl) plus 1:100,000 epinephrine (A100) with those of 11.9 mL of 4 percent articaine HCl plus 1:200,000 epinephrine (A200). METHODS: During two testing sessions, the authors administered injections of A100 and A200 over a seven-minute period (in one-cartridge doses unless otherwise noted): maxillary right first molar infiltration, maxillary left first molar infiltration, maxillary right first premolar infiltration, maxillary left first premolar infiltration, right inferior alveolar injection, left inferior alveolar injection, right long buccal infiltration (one-half cartridge) and left long buccal infiltration (one-half cartridge). They analyzed venous blood samples for articaine levels. They used noninvasive acoustic tonometry to measure a variety of cardiovascular parameters over a two-hour period. RESULTS: Plasma concentration curves of articaine over time were similar for both solutions, with peak concentrations and times to maximum concentration being 2,037 nanograms per milliliter and 22 minutes for A100 and 2,145 ng/mL and 22 minutes for A200. At the 10-minute point, the mean systolic blood pressure and heart rate were significantly elevated (P < .05) with A100 versus A200. CONCLUSIONS: Maximum dose recommendations for the A100 solution also can be applied to the A200 solution. A200 produces less cardiovascular stimulation than does A100. CLINICAL IMPLICATIONS: A200 is as safe as A100, and may be preferable to A100 in patients with cardiovascular disease and in those taking drugs that reportedly enhance the systemic effects of epinephrine.

Selection of local anesthetics in dentistry: clinical impression versus scientific assessment.

Since its introduction to in the United States about six years ago, 4% articaine with 1:200,000 epinephrine has been used by dentists as a local anesthetic agent. This article reviews three claims that have been advanced regarding articaine: high diffusibility, reduced incidence of failure in block injections, and effectiveness in achieving anesthesia when used in cases involving irreversible pulpitis.

Clinical pharmacokinetics of articaine.

Articaine is the most widely used local anaesthetic agent in dentistry in a number of European countries. The amide structure of articaine is similar to that of other local anaesthetics, but it contains an additional ester group which is quickly hydrolysed by esterases. High performance liquid chromatography has been used to determine the concentrations of articaine and its metabolite articainic acid in serum. Rapid sample preparation is critical in the accurate determination of articaine serum concentrations, since blood and serum are the sites of metabolism. The time to maximum drug concentrations of articaine occurs about 10 to 15 minutes after submucosal injection of articaine 4% 80 mg, irrespective of epinephrine (adrenaline). The mean maximum plasma drug concentration is about 400 micrograms/L for articaine with epinephrine 1:200,000 and 580 micrograms/L for articaine without epinephrine. The elimination half-time of articaine is about 20 minutes. The rapid breakdown of articaine to the inactive metabolite articainic acid is related to a very low systemic toxicity and consequently to the possibility of repeated injections. Equal analgesic efficacy along with lower systemic toxicity (i.e. a wide therapeutic range) permits the use of articaine in higher concentrations than other amide-type local anaesthetics. Complete anaesthesia can be observed in nearly 90% of all cases, using articaine 4% 60 to 80 mg with epinephrine 1:200,000. Articaine is better able to diffuse through soft tissue and bone than other local anaesthetics. The concentration of articaine in the alveolus of a tooth in the upper jaw after extraction was about 100 times higher than that in systemic circulation. The plasma protein binding rate of articaine and articainic acid is 70%. It has been concluded that an unintentional intravascular injection of articaine 80 mg does not cause toxic effects in healthy individuals.

Pharmacokinetics of articaine hydrochloride in tumescent local anesthesia for liposuction.

The aim of the investigation was to assess the pharmacokinetic characteristics and safety of articaine HCl used in tumescent local anesthesia for liposuction. Maximum plasma concentrations of articaine HCl were observed from 136 to 264 ng/mL, on average, from 1.2 to 4.3 hours after the start of infiltration, depending on the area of liposuction. The average extent of absorption ranged from 827 to 2203 ng*h/mL. Average maximum plasma concentrations of articainic acid ranged from 1719 to 7292 ng/mL. The high articainic acid concentrations at 1 hour after the start of infiltration indicate that articaine HCl was hydrolyzed rapidly by esterases in tissue and plasma. Although up to 38.2 mg/kg body weight articaine HCl was applied, no cardiac side effects or symptoms of central nervous intoxication occurred. Articaine HCl provided a safe and sufficient analgesia for tumescent liposuction.

Similar motor block effects with different disposition kinetics between lidocaine and (+ or -) articaine in patients undergoing axillary brachial plexus block during day case surgery.

AIM: The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine and articaine in two groups of 15 patients undergoing axillary brachial plexus anesthesia. METHOD: The study had a randomized design. Thirty patients were allocated to one of the two groups. Each patient received either lidocaine (600 mg = 2.561 mMol + 5 microg/ml adrenaline) or articaine (600 mg = 2.113 mMol + 5 microg/ml adrenaline), injected via the axilla of the brachial plexus over a period of 30 seconds. Onset of surgical analgesia was defined as the period from the end of the injection of the local anesthetic to the loss of pinprick sensation in the distribution of all three nerves. RESULTS: The mean onset time of sensory block of the median nerve of both lidocaine and articaine were approximately 10 min. Lidocaine is biexponentially eliminated with a t1/2alpha of 9.95 +/- 14.3 min and a t1/2beta of 2.86 +/- 1.55 h. Lidocaine is metabolized into MEGX (mono-ethyl-glycyl-xilidide) (t(max) 2.31 +/- 0.84 h; C(max) 0.32 +/- 0.13 mg/l; t1/2beta 2.36 +/- 2.35 h). Lidocaine total body clearance was 67.9 +/- 28.9 l/h. Articaine is rapidly and monoexponentially eliminated with a t1/2beta of 0.95 +/- 0.39 h. The total body clearance of articaine is higher than that of lidocaine, 1,133 +/- 582 l/h vs 67.9 +/- 28.9 l/h, respectively (p < 0.0001). The volume of distribution (V(d)), of articaine is a factor 16 higher times than that of lidocaine (p < 0.0001). CONCLUSION: For the axillary administration, lidocaine and articaine show similar pharmacodynamics with a different pharmacokinetic behavior and can therefore be used to the clinical preference for this regional anesthetic technique.

The effect of age on pharmacokinetics of the local anesthetic drug articaine.

BACKGROUND AND OBJECTIVES: With increasing age, there are physiologic changes that could affect pharmacokinetics of drugs. More elderly patients are undergoing routine dental procedures for which local anesthesia could be required. The goal of the present study was to evaluate the effect of age on pharmacokinetics of the local anesthetic agent articaine. METHODS: The submucosal infiltration anesthesia from two different dosages of 4% articaine without epinephrine was compared in healthy elderly and young volunteers. High performance liquid chromatography has been used to determine concentrations of articaine in serum. Basic pharmacokinetic parameters were calculated according to standard procedures using a two-exponent equation. RESULTS: The clearance and volume of distribution (Vdss) of articaine after infiltration anesthesia were significantly lower in elderly volunteers compared with young volunteers. The area under the serum concentration-time curve and maximum drug concentration (Cmax) values did not differ significantly with age; however, both parameters tended to be higher in elderly volunteers. No changes in terminal half-life and time to reach maximum serum concentration (t(max)) were observed. The Cmax and tmax values of the metabolite articainic acid were similar in young and elderly volunteers. CONCLUSIONS The results show that the metabolism of articaine is age-independent in healthy male volunteers. The smaller Vdss in the elderly results in a trend to higher serum levels after a given dose of articaine. No change of dosage of articaine in elderly patients should be necessary.

Epidural metabolism of articaine to its metabolite articainic acid in five patients after epidural administration of 600 mg articaine.

The clinical pharmacokinetics, metabolism and renal excretion of articaine and its metabolite articainic acid have been investigated in man after epidural administration. (+/-)-Articaine and its metabolite (+/-)-articainic acid have different pharmacokinetic constants (P = 0.0079) except for lag-time (tlag; 0.06 min), first phase distribution of elimination (t 1/2 alpha; 0.49 +/- 0.21 h), and elimination half life (t 1/2 beta; 2.19 +/- 0.98 h), which are all the same for both compounds. The total body clearance of articaine (103 +/- 57 L h-1) is 10 times higher than that of the metabolite articainic acid (10.7 +/- 1.80 L h-1, P = 0.0079). With similar half-life (t 1/2 beta) values (2h), the volumes of distribution (V beta) are 10 times higher for the parent drug than for the metabolite ((329 +/- 212 L compared with 38.4 +/- 7.5 L, respectively; P = 0.0079). The difference between the areas under the curves for total plasma articainic acid and that formed in the plasma gives an indication of the percentage metabolism during epidural transfer (5.38 +/- 1.51%). This percentage of metabolism corresponds to a mean epidural transfer time of 5 min. The main compound in the urine is articainic acid (64.2 +/- 14.4%), followed by articainic acid glucuronide (13.4 +/- 4.97%) and the parent drug (1.45 +/- 0.77%). In total, 79.0 +/- 18.5% of the dose is recovered in the urine. The renal clearance of articaine is 22.5 +/- 13.9 mL min-1, whereas that of articainic acid is 119.6 +/- 30.1 mL min-1 (P < 0.0001). The apparent renal clearance of articainic acid glucuronide was 25.4 +/- 12.0 mL min-1. This value does not differ from that of the parent drug (P > 0.8). Articainic acid glucuronide is not present in plasma, but has an apparent renal clearance of 25 mL min-1. These results suggest that articainic acid is glucuronidated by the tubular cells and then excreted.

Serum levels of articaine 2% and 4% in children.

The results of the present study of the pharmacokinetics of articaine in children show serum concentrations comparable to those in adults. The maximum values are distinctly lower with the 2% articaine solution. The t max found in our investigation was distinctly earlier than in comparable investigations on adults, whereas the plasma clearance was increased. There is no need to fix a lower mg/kg articaine dose limit for children because of age-related differences in the pharmacokinetics. The use of 2% articaine in pediatric dentistry is particularly advantageous because of the lower C max and the shorter half-life.

[Pharmacology of local anesthetics and clinical aspects of segment blockade. I. Epidural anesthesia]. / Farmakologiia mestnykh anestetikov i klinika segmentarnykh blokad: I. Epidural'naia anesteziia.

Clinical pharmacology of three local anesthetics is studied. Seventy-five patients operated on under epidural anesthesia with 2% lidocaine solution, citanest, and ultracaine without adrenalin were examined. Lidocaine and ultracaine ensured a more rapid development of the epidural block (12.1 +/- 1.2 and 11.1 +/- 1.5 min, respectively) in comparison with citanest (15.4 +/- 1.1 min, p < 0.05). Lesser doses of ultracaine are needed for the development of a sensory block of the same extent than of lidocaine (1.7 +/- 0.05 and 2.2 +/- 0.2 ml per segment, respectively, p < 0.05). Citanest dose (in solution) is intermediate: 1.9 +/- 0.15 ml per segment. Ultracaine and citanest provide a more profound sensory block in comparison with lidocaine. However, there were 16% of incomplete ("mosaic") anesthesias in the citanest group. The duration of sensory blocking was the maximal in the citanest group (107.1 +/- 7.1 min), ultracaine ranked second (94 +/- 4.4 min, p < 0.05), and lidocaine third (70.6 +/- 4.0 min, p < 0.05). The authors discuss the clinical picture of epidural blocking by different anesthetics and compare their physicochemical characteristics.

Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: a molecular dynamics study.

Local anesthetics (LAs) are drugs that cause reversible loss of nociception during surgical procedures. Articaine is a commonly used LA in dentistry that has proven to be exceptionally effective in penetrating bone tissue and induce anesthesia on posterior teeth in maxilla and mandibula. In the present study, our aim was to gain a deeper understanding of the penetration of articaine through biological membranes by studying the interactions of articaine with a phospholipid membrane. Our approach involves Langmuir monolayer experiments combined with molecular dynamics simulations. Membrane permeability of LAs can be modulated by pH due to a titratable amine group with a pKa value close to physiological pH. A change in protonation state is thus known to act as a lipophilicity switch in LAs. Our study shows that articaine has an additional unique lipophilicity switch in its ability to form an intramolecular hydrogen bond. We suggest this intramolecular hydrogen bond as a novel and additional solvent-dependent mechanism for modulation of lipophilicity of articaine which may enhance its diffusion through membranes and connective tissue.