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Journal of Medical Toxicology :... Mar 2010Dibucaine is a potent, long-lasting local anesthetic (LA). Topical dibucaine ointments are marketed directly to consumers in the USA without prescription. Dibucaine...
INTRODUCTION
Dibucaine is a potent, long-lasting local anesthetic (LA). Topical dibucaine ointments are marketed directly to consumers in the USA without prescription. Dibucaine ointment is intended to treat discomfort associated with sunburn, eczema, minor rashes, minor scratches, insect bites, and poison ivy and is used alone or in combination with other active ingredients to treat pain associated with hemorrhoids or other anorectal disorders. Oral dibucaine toxicosis has been reported in children and includes gastrointestinal upset and neurologic and cardiovascular dysfunction.
CASE REPORT
An 18-month-old, female, Parson Russell terrier ingested approximately 23 g of 1% dibucaine ointment (approximately 38 mg/kg dibucaine) recommended to the owner for the treatment of hemorrhoids. Onset and resolution of clinical signs were relatively rapid, 5 min and 60 min, respectively. Clinical signs included vomiting, ptyalism, whole-body muscle fasciculations, disorientation, and severe ataxia.
DISCUSSION
Oral dibucaine toxicosis in dogs is similar to oral dibucaine toxicosis in children. Dibucaine ointment poses a real and potentially serious toxicological risk to pets and thus should be stored in a safe location.
Topics: Accidents; Administration, Oral; Anesthetics, Local; Animals; Antidotes; Ataxia; Charcoal; Confusion; Dibucaine; Dog Diseases; Dogs; Female; Poisoning; Sialorrhea; Spasm; Treatment Outcome; Vomiting
PubMed: 20224995
DOI: 10.1007/s13181-010-0036-3 -
Journal of Pharmaceutical Sciences Sep 2018Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the...
Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.
Topics: Anesthetics, Local; Animals; BALB 3T3 Cells; Cell Survival; Dibucaine; Drug Liberation; Liposomes; Male; Mice; Motor Activity; Pain Measurement; Phosphatidylcholines; Zebrafish
PubMed: 29802933
DOI: 10.1016/j.xphs.2018.05.010 -
Journal of Liposome Research Sep 2021We have previously developed ammonium sulphate gradient loaded liposomes to encapsulate dibucaine. Thus, the purpose of this study was to evaluate the pre-clinical...
We have previously developed ammonium sulphate gradient loaded liposomes to encapsulate dibucaine. Thus, the purpose of this study was to evaluate the pre-clinical safety and effectiveness of this novel ionic liposomal formulation of dibucaine (DBC), as described in previous work. Effectiveness was evaluated on Wistar rats (n = 8) that received plain DBC or liposomal DBC (DBC). Control empty liposomes (without DBC) or saline were also used as control. Sciatic nerve block was performed using the formulations or controls (0.4 mL). A hindpaw incision-based postoperative pain model was used to evaluate mechanical hypersensitivity with von Frey filaments. To verify antiinflamatory activity protein levels of TNF-α, IL-1β, substance P and CGRP were measured by ELISA in the hindpaw tissue after 1 and 6 hours of the incision. To corroborate drug safety, sciatic nerve Schwann cell cultures were treated with the aforementioned formulations and assessed for cell viability (MTT assay) and death (flow cytometry assay). Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. All animals presented post incisional hypersensitivity and DBC showed longer analgesic effect ( < 0.001). DBC reduced TNF-α and CGRP levels ( < 0.05). Histopathological evaluation showed greater inflammatory reaction after the administration of control liposomes when compared to DBC ( < 0.05). There was no difference in Schwann cell viability and death between plain and encapsulated DBC. DBC was safe and enhanced anaesthesia duration due to slow release of dibucaine from ammonium sulphate gradient loaded liposomes.
Topics: Analgesia; Anesthetics, Local; Animals; Dibucaine; Liposomes; Rats; Rats, Wistar
PubMed: 32567452
DOI: 10.1080/08982104.2020.1785494 -
Cell Biology International Reports Apr 1990The interaction between lipids and water soluble amphiphiles was investigated by means of a monolayer technique, monitoring the area increase at constant surface... (Review)
Review
The interaction between lipids and water soluble amphiphiles was investigated by means of a monolayer technique, monitoring the area increase at constant surface pressure. The area increase could be quantitated and binding isotherms at different surface pressures were measured. A comparison of dibucaine binding to monolayers and bilayers showed that a surface pressure of 32 mN/m best represents the packing density in a lipid bilayer (Seelig, 1987). Binding isotherms measured for charged dibucaine and substance P (SP) were analyzed by means of two different models. If electrostatic effects were ignored the binding of dibucaine and SP showed biphasic Scatchard plots. If, however, electrostatic effects were taken into account by means of the Gouy-Chapman theory, the insertion of both amphiphiles was best described in terms of a partitioning into the monolayer lipids. The hydrophobic binding constant was Kp = 660 +/- 80 M-1 for charged dibucaine inserting into coarse liposomes or monolayers at 32 mN/m (Seelig et al., 1986) and 1-1.8 M-1 for SP inserting into monolayers at 32 mN/m (Seelig and Macdonald, 1989).
Topics: Dibucaine; Lipid Metabolism; Mathematics; Substance P
PubMed: 1693884
DOI: 10.1016/0309-1651(90)91206-j -
Biomedicine & Pharmacotherapy =... Aug 2023Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for...
Novel treatment and insight for irradiation-induced injuries: Dibucaine ameliorates irradiation-induced testicular injury by inhibiting fatty acid oxidation in primary Leydig cells.
BACKGROUND
Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for the treatment of irradiation-induced testicular injury.
METHODS
We administered dibucaine (0.8 mg/kg) intraperitoneally to male mice (6 mice per group) after five consecutive daily 0.5 Gy whole-body irradiation, and evaluated its ameliorating efficacy by testicular HE staining and morphological measurements. Drug affinity responsive target stability assay (Darts) were used to find target protein and pathway; mouse primary Leydig cells were isolated and to explore the mechanism (Flow cytometry, Western blot, and Seahorse palmitate oxidative stress assays); finally rescue experiments were completed by combining dibucaine with fatty acid oxidative pathway inhibitors and activators.
RESULTS
The testicular HE staining and morphological measurements in dibucaine treatment group was significantly better than that in irradiation group (P < 0.05); sperm motility and mRNA levels of spermatogenic cell markers were also higher than those in the latter (P < 0.05). Darts and Western blot results showed that dibucaine targets CPT1A and downregulate fatty acid oxidation. Flow cytometry, Western blot, and Palmitate oxidative stress assays of primary Leydig cells demonstrated that dibucaine inhibits fatty acid oxidation in Leydig cells. Dibucaine combined with etomoxir/baicalin confirmed that its inhibition of fatty acid oxidation was beneficial in ameliorating irradiation-induced testicular injury.
CONCLUSIONS
In conclusion, our data suggest that dibucaine ameliorates irradiation-induced testicular injury in mice by inhibiting fatty acid oxidation in Leydig cells. This will provide novel ideas for the treatment of irradiation-induced testicular injury.
Topics: Humans; Male; Mice; Animals; Leydig Cells; Dibucaine; Sperm Motility; Testis; Testicular Diseases; Fatty Acids; Palmitates
PubMed: 37224756
DOI: 10.1016/j.biopha.2023.114903 -
Biochimica Et Biophysica Acta.... Jun 2019Mitochondrial membranes are pointed out as the site of cardiotoxic action of local anaesthetics. Its three main phospholipids components are phosphatidylcholine,...
Mitochondrial membranes are pointed out as the site of cardiotoxic action of local anaesthetics. Its three main phospholipids components are phosphatidylcholine, phosphatidylethanolamine and cardiolipin. Cardiolipins, in eukaryotes, are only found in mitochondria and are essential for the maintenance of its integrity and dynamics. Fluorescence and nuclear magnetic resonance spectroscopy were used to study the interactions of a local anaesthetics, Dibucaine (DBC), with different mitochondrial membrane models constituted by combinations of its three main lipid components in which cardiolipin was a natural extract (CL). Both CL presence/absence and its percentage in the model membranes were evaluated. Fluorescence spectroscopy showed that DBC lowered the transition temperature of all membrane models understudy. DBC partition showed to be dependent of CL presence and phosphatidylethanolamine:CL ratio. Furthermore, the maximum emission wavelength (λ) exhibited a notorious decreased with increasing phospholipid to DBC ratio, in all the membrane models containing CL. Nevertheless, it remained approximately the same in the membrane without CL. This indicates a differential membrane localization of the anaesthetics, dependent on the membrane models used. NMR results showed that DBC interaction and location in the membrane models is mainly influenced by CL presence, and DBC can significant alter lipid systems properties e.g. percentage and type of lipid phase present. Taken all together it was shown that DBC interaction and location are largely dependent on the membrane model system. Furthermore, DBC is able to produce significant changes in the lipidic systems which might help to explain its high toxicity.
Topics: Anesthetics, Local; Binding Sites; Cardiolipins; Dibucaine; Mitochondrial Membranes; Models, Biological; Phosphatidylethanolamines; Temperature
PubMed: 30840858
DOI: 10.1016/j.bbamem.2019.02.011 -
Chemical Research in Toxicology Feb 2011A wide range of cationic amphiphilic drugs (CADs) from different therapeutic areas are known to cause phospholipidosis both in vivo and in vitro. Although the relevance...
A wide range of cationic amphiphilic drugs (CADs) from different therapeutic areas are known to cause phospholipidosis both in vivo and in vitro. Although the relevance of this storage disorder for human health remains uncertain, CADs have been repeatedly associated with clinical side effects, and as a result, phospholipidosis is of major concern for drug development in the pharmaceutical industry. An important unresolved question in this field is whether phospholipidosis is really linked to cellular toxicity. This work was focused on studying cellular responses associated with CAD-induced phospholipidosis in cultured mammalian kidney cells. Dibucaine (2-butoxy-N-[2-diethylaminoethyl]quinoline-4-carboxamide), an amide-type anesthetic with poorly defined cytotoxic effects, was used to induce phospholipidosis in Vero cells. The results from several assays that measure cell viability, proliferation, and morphological changes indicated that dibucaine-induced lysosomal phospholipidosis was accompanied by cellular defense responses such as transient growth arrest and autophagy, under mild stress conditions. Conversely, when tolerance limits were exceeded treated Vero cells underwent extensive and irreparable injury, leading ultimately to cell death. Our data provide additional information that may be of considerable interest for drug safety assessment.
Topics: Anesthetics, Local; Animals; Cell Proliferation; Cell Survival; Chlorocebus aethiops; Dibucaine; Lipidoses; Lysosomes; Phospholipids; Vero Cells
PubMed: 21261262
DOI: 10.1021/tx100262c -
Biochimica Et Biophysica Acta Jan 1994The location of molecules of the local anesthetic dibucaine in sarcoplasmic reticulum vesicles (SRV) was determined using the quenching of its intrinsic fluorescence by...
The location of molecules of the local anesthetic dibucaine in sarcoplasmic reticulum vesicles (SRV) was determined using the quenching of its intrinsic fluorescence by iodide and by nitroxide-labeled stearic acids (SASL) with the nitroxide group at different positions of the fatty acyl chain. The molar ratios of dibucaine to Ca(2+)-ATPase in the samples were less than 1. The acid-base titration of membrane bound dibucaine revealed a pK of 9.1, showing a negligible shift upon binding. The quenching data were obtained at pH 6.8 and are therefore related to protonated dibucaine. Quenching by iodide showed SRV-bound dibucaine to be more protected from collisions with iodide anion than dibucaine in buffer or even in neutral micelles. This shows the influence of negatively charged lipids in keeping iodide away from the ionic diffuse layer of the membrane surface where the dibucaine tertiary amine might be located. Analysis of the SASL quenching data indicates that dibucaine molecules are at a shallow position in the membrane bilayer. Their average depth was found to be at most that of the fourth carbon atom of the fatty acyl chain. The results do not exclude a preferential site for dibucaine in Ca(2+)-ATPase, but if there is such site it must be located at the protein/lipid interface.
Topics: Animals; Binding Sites; Buffers; Dibucaine; Hydrogen-Ion Concentration; Lipid Bilayers; Rabbits; Sarcoplasmic Reticulum; Sodium Iodide; Spectrometry, Fluorescence; Stearic Acids
PubMed: 8292630
DOI: 10.1016/0005-2736(94)90071-x -
Cell Biology International Reports Jan 1977Synchronous secretion of all available mature mucocysts was induced in late log phase cultures of Tetrahymena thermophilia (B III) by the local anaesthetic dibucaine. No...
Synchronous secretion of all available mature mucocysts was induced in late log phase cultures of Tetrahymena thermophilia (B III) by the local anaesthetic dibucaine. No assembled fusion rosettes were seen within the plasma membrane after release until 2-3 hrs of regrowth, thus proving that the rosettes are not permanent sites within the plasma membrane but have to be reassembled each time for a new fusion event to occur. Concomitant with the reappearance of assembled fusion rosettes, the cell cytoplasm fills up with precursors of new mucocysts thus linking the two events together.
Topics: Animals; Cell Membrane; Dibucaine; Exocytosis; Freeze Fracturing; Tetrahymena
PubMed: 610868
DOI: 10.1016/0309-1651(77)90012-1 -
Anaesthesia Apr 1969
Topics: Anesthesia, Spinal; Dibucaine; Drug and Narcotic Control; Economics; Humans; Lidocaine; Procaine; Tetracaine
PubMed: 5774706
DOI: No ID Found