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Anesthesiology May 1977
Topics: Anesthesia, Spinal; Densitometry; Dibucaine; Humans; Tetracaine
PubMed: 851253
DOI: 10.1097/00000542-197705000-00023 -
The Biochemical Journal Feb 19771. Virally mediated permeability changes are not brought about by neuraminidase or other enzyme. They are not mimicked by local anaesthetics such as benzyl alcohol or...
1. Virally mediated permeability changes are not brought about by neuraminidase or other enzyme. They are not mimicked by local anaesthetics such as benzyl alcohol or dibucaine. 2. Virus induces an increase in the exchange rate of membrane-bound Ca2+. The temperature-dependence, and sensitivity to concanavalin A, of the permeability change and of Ca2+ exchange are similar. 3. It is concluded that an increase in the exchangeability of membrane-bound Ca2+ constitutes an early and specific event after the attachment of Sendai virus to cultured cells.
Topics: Calcium; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Concanavalin A; Dibucaine; Neuraminidase; Parainfluenza Virus 1, Human; Temperature
PubMed: 192222
DOI: 10.1042/bj1620405 -
British Journal of Pharmacology Apr 2001AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+) channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to...
AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+) channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na(+) channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neuronal death in the penumbra of the ischaemic lesion is suggested to occur by apoptosis, we investigated the ability of AM-36, antioxidants and Na(+) channel antagonists to inhibit toxicity induced by the neurotoxin, veratridine in cultured cerebellar granule cells (CGC's). Veratridine (10 - 300 microM) concentration-dependently reduced cell viability of cultured CGC's. Under the experimental conditions employed, cell death induced by veratridine (100 microM) possessed the characteristics of apoptosis as assessed by morphology, TUNEL staining and DNA laddering on agarose gels. Neurotoxicity and apoptosis induced by veratridine (100 microM) were inhibited to a maximum of 50% by the antioxidants, U74500A (0.1 - 10 microM) and U83836E (0.03 - 10 microM), and to a maximum of 30% by the Na(+) channel blocker, dibucaine (0.1 - 100 microM). In contrast, AM-36 (0.01 - 10 microM) completely inhibited veratridine-induced toxicity ( IC(50) 1.7 (1.5 - 1.9) microM, 95% confidence intervals (CI) in parentheses) and concentration-dependently inhibited apoptosis. These findings suggest veratridine-induced toxicity and apoptosis are partially mediated by generation of ROS. AM-36, which combines both Na(+) channel blocking and antioxidant activity, provided superior neuroprotection compared with agents possessing only one of these actions. This bifunctional profile of activity may underlie the potent neuroprotective effects of AM-36 recently found in a stroke model in conscious rats.
Topics: Animals; Apoptosis; Cell Survival; Cells, Cultured; DNA Fragmentation; Depression, Chemical; Dibucaine; Electrophoresis, Agar Gel; Free Radical Scavengers; Immunohistochemistry; In Situ Nick-End Labeling; Mice; Neurons; Neuroprotective Agents; Piperazines; Sodium Channel Agonists; Sodium Channel Blockers; Tetrodotoxin; Veratridine
PubMed: 11309240
DOI: 10.1038/sj.bjp.0704018 -
Acta Poloniae Pharmaceutica 2005Formulation of local anesthetics in liposomal topical drug delivery system could provide a sustained and localized anesthesia. The aim of this study was to develop a...
Formulation of local anesthetics in liposomal topical drug delivery system could provide a sustained and localized anesthesia. The aim of this study was to develop a liposomal dibucaine base (DB) local anesthetic delivery system. DB-loaded multilamellar vesicles (MLVs) were prepared through varying lipid composition, induced charge and pH of the hydration medium. Liposomes were characterized for morphology, size, entrapment efficiency (EE), in vitro drug release and stability including leakage stability. The percentage of drug entrapped in liposomes was found to be hydration medium pH dependent and charge dependent and more pronounced for negatively charged liposomes prepared using hydration medium of pH 9. In vitro release studies of liposomes have shown a sustained release of entrapped dibucaine compared to control solution. Results revealed that adjusting the various formulation variables of dibucaine base MLVs could yield stable and effective topical liposomal local anesthetic formulations.
Topics: Anesthetics, Local; Chemistry, Pharmaceutical; Dibucaine; Drug Compounding; Drug Stability; Liposomes; Membranes, Artificial
PubMed: 16459486
DOI: No ID Found -
Japanese Journal of Pharmacology Jan 1985Procaine (1 X 10(-5)-1 X 10(-4) M), dibucaine (1 X 10(-5)-1 X 10(-4) M) and tetracaine (1 X 10(-6)-1 X 10(-5) M) caused an increase followed by a decrease in the rate of...
The effects of tetrodotoxin, papaverine and verapamil on the increase in the rate of spontaneous afferent discharges induced by local anesthetics from the pulmonary mechanoreceptors of the bullfrog.
Procaine (1 X 10(-5)-1 X 10(-4) M), dibucaine (1 X 10(-5)-1 X 10(-4) M) and tetracaine (1 X 10(-6)-1 X 10(-5) M) caused an increase followed by a decrease in the rate of spontaneous afferent (A) discharges (D) accompanied with a decrease in the flow rate of perfusion solution from the pulmonary vein in the isolated lung of the bullfrog, but these local anesthetics only decreased the rate of A.D. synchronized with lung inflation. The stimulatory effects of these drugs on the rate of spontaneous A.D. were studied. In the presence of TTX (1 X 10(-7) M), the increase in the rate of spontaneous A.D. by local anesthetics was inhibited, but the decrease in the flow rate of perfusion solution by these drugs was not inhibited. Papaverine (1 X 10(-5) M), which inhibited the decrease in the flow rate of perfusion solution by these local anesthetics, inhibited the increase in the rate of spontaneous A.D. by dibucaine, but not those by procaine and tetracaine. The inhibitory effects on the increase in the rate of spontaneous A.D. by these local anesthetics could be seen with verapamil in a concentration (1 X 10(-4) M) which significantly inhibited the rate of spontaneous A.D., like TTX (1 X 10(-7) M). Verapamil could not reverse the decrease in the flow rate of perfusion solution by these local anesthetics. From these result, the increase in the rate of spontaneous A.D. by procaine and tetracaine is due to not only the contractile effects of the drugs on the pulmonary vessel but also the direct stimulatory effects on the receptors which generate spontaneous A.D., and the increase in the rate of spontaneous A.D. by dibucaine may result from the contraction of the pulmonary vessel, and the stimulatory effect of dibucaine on the receptors would be weaker than that of procaine and tetracaine, since dibucaine could cause the increase in the rate of spontaneous A.D. only when dibucaine decreased the flow rate of perfusion solution.
Topics: Aconitine; Action Potentials; Anesthetics, Local; Animals; Dibucaine; In Vitro Techniques; Lung; Mechanoreceptors; Neurons, Afferent; Papaverine; Procaine; Rana catesbeiana; Tetracaine; Tetrodotoxin; Verapamil
PubMed: 3872956
DOI: 10.1254/jjp.37.1 -
The Biochemical Journal Aug 19901. The flux pathways for H+ and K+ movements into and out of proteoliposomes incorporating cytochrome c oxidase have been investigated as a function of the electrical...
1. The flux pathways for H+ and K+ movements into and out of proteoliposomes incorporating cytochrome c oxidase have been investigated as a function of the electrical and geometrical properties of the vesicles. 2. The respiration-induced pH gradient (delta pH) and membrane potential (delta psi) are mutually dependent and individually sensitive to the permeability properties of the membrane. A lowering or abolition of delta psi by the addition of valinomycin increased the steady-state level of delta pH. Conversely, removal of delta pH by the addition of nigericin resulted in a higher steady-state delta psi. 3. Vesicles prepared by sonication followed by centrifugation maintained similar pH gradients at steady state to those in vesicles prepared by dialysis, although the time taken to reach steady state was longer. Higher pH gradients can be induced in non-centrifuged sonicated preparations. 4. No significant differences were found in H+ and K+ permeability between proteoliposomes prepared by dialysis or by sonication. The permeability coefficient of the vesicle bilayers for H+ was 6.1 x 10(-4) cm.s-1 and that for K+ was 7.5 x 10(-10) cm.s-1. An initial fast change in internal pH was seen on the addition of external acid or alkali, followed by a slower, ionophore-sensitive, change. The initial fast phase can be increased by the lipid-soluble base dibucaine and the weak acid oleate. In the absence of ionophores, increasing concentrations of oleate increased the rate of H+ translocation to a level similar to that seen in the presence of nigericin. Internal alkalinization could also be induced by oleate upon the addition of potassium sulphate. 5. The initial, pre-steady-state and steady-state delta pH and delta psi changes can be simulated using a model in which the enzyme responds to both delta pH and delta psi components of the protonmotive force. At steady state, the electrogenic entry of K+ is countered by electroneutral exit via a K+/H+ exchange. 6. The permeability coefficient, PH, calculated from H+ flux under steady-state turnover conditions, was approx. 100 times higher than the corresponding 'passive' measurements of PH. Under conditions of oxidase turnover, the vesicles appear to be intrinsically more permeable to protons.
Topics: Animals; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Cattle; Cell Membrane; Dibucaine; Electron Transport Complex IV; Hydrogen-Ion Concentration; In Vitro Techniques; Ionophores; Membrane Potentials; Models, Theoretical; Oleic Acid; Oleic Acids; Permeability; Proteolipids; Protons; Valinomycin
PubMed: 2168698
DOI: 10.1042/bj2700109 -
Anesthesiology Oct 1980A rapid, reliable method for the determination of 2-chloroprocaine in serum was developed. The method, using double-beam ultraviolet spectroscopy, provides rapid,...
A rapid, reliable method for the determination of 2-chloroprocaine in serum was developed. The method, using double-beam ultraviolet spectroscopy, provides rapid, accurate analysis of 2-chloroprocaine in the range of 5.5 to 111 microM (1.5--30 microgram/ml), as documented by comparison with the accepted gas chromatographic procedure. The contribution of 4-amino-2-chlorobenzoic acid, the principal metabolite of 2-chloroprocaine, to the total absorbance at 300 nm was examined and found to be negligible. Using the ultraviolet spectrophotometric method, values of the Michaelis-Menton constant (Km) and maximal reaction velocity (Vmax) for hydrolysis of procaine and 2-chloroprocaine by homozygous typical, heterozygous, and homozygous atypical plasma cholinesterase were determined. The Kms for the three genotypes were 5.0, 6.2, and 14.7 microM, respectively, for procaine, and 8.2, 17, and 103 microM, respectively for 2-chloroprocaine. The Vmaxs for the three genotyps were similar for all esters. Vmax for procaine was 18.6 +/- 0.9 nmol/min/ml serum, while Vmax for 2-chloroprocaine was 98.4 +/- 2.1 nmol/min/ml serum. At high concentrations, 2-chloroprocaine acts as an inhibitor of its hydrolysis. The inhibitory effects of lidocaine, bupivacaine, neostigmine, and succinyldicholine on 2-chloroprocaine hydrolysis for homozygous typical and atypical variants, respectively, were studied. Competitive inhibition was demonstrated for all four drugs. However, at clinically significant concentrations, only neostigmine and bupivacaine produced high degrees of inhibition. The competitive inhibition constants (K1) for the typical and atypical variants, respectively, were 3.3 +/- 0.3 microM and 15.1 +/- 4.8 microM for neostigmine, and 4.2 +/- 0.3 microM and 36.9 +/- 9.8 microM for bupivacaine.
Topics: Adjuvants, Pharmaceutic; Anesthetics; Benzoylcholine; Chlorobenzoates; Chromatography, Gas; Dibucaine; Esters; Hydrolysis; Kinetics; Procaine; Spectrum Analysis; Succinylcholine
PubMed: 7425357
DOI: 10.1097/00000542-198010000-00007 -
Anesthesiology Dec 1981Determination of the dibucaine number of serum permits the differentiation of genetically normal serum cholinesterase from the dibucaine-resistant variant. This...
Determination of the dibucaine number of serum permits the differentiation of genetically normal serum cholinesterase from the dibucaine-resistant variant. This communication presents a method for the rapid determination of dibucaine numbers on an automated analyzer that is in widespread use. With this method, dibucaine numbers for seventy-eight normal, four heterozygous, and five dibucaine-resistant sera were 79 +/- 3,60 +/- 10, and 20 +/- 3 (+/- SD), respectively. There was good agreement between the original method and the automated method with a correlation coefficient of 0.98 on split sample comparison of thirty-eight normal, four heterozygous, and five abnormal sera. Advantages of this method over the original include the lack of need for advance preparation and that it can provide results within one-half hour of phlebotomy.
Topics: Autoanalysis; Cholinesterases; Dibucaine; Enzyme Inhibitors; Genetic Variation; Humans
PubMed: 7305055
DOI: 10.1097/00000542-198155060-00012 -
Anesthesiology Oct 1995Mivacurium chloride is a bis-benzylisoquinolinium nondepolarizing neuromuscular blocking agent, hydrolyzed by butyrylcholinesterase (PCHE). The dose-response... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Mivacurium chloride is a bis-benzylisoquinolinium nondepolarizing neuromuscular blocking agent, hydrolyzed by butyrylcholinesterase (PCHE). The dose-response relationships for PCHE after mivacurium have not been studied. Therefore, this study was designed to establish dose-response relationships for PCHE as an antagonist of mivacurium-induced neuromuscular blockade.
METHODS
Forty-eight physical status 1 adults were given 0.15 mg/kg mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height (T1) reached 10% of its initial control value, exogenous PCHE equivalent to activity present in 2.5, 5, 7.5, 15, or 25 ml/kg of human plasma was administered by random allocation to 40 patients. Neuromuscular function in another eight subjects was allowed to recover spontaneously. Two blood samples were taken for determination of plasma cholinesterase activity. The first sample was taken before induction of anesthesia, and the second sample was taken when the TOF ratio had recovered to 0.75. Dibucaine and fluoride numbers were determined from the first assay.
RESULTS
Administration of PCHE produced significant increases in PCHE activity in all patients. The larger the dose, the greater was the resultant plasma activity. Human PCHE produced a dose-dependent antagonism of mivacurium-induced neuromuscular blockade and the recovery times correlated inversely with PCHE activity (P < 0.01). The recovery of T1 was greater (P < 0.01) and time to attain a TOF ratio of 0.75 was shorter (P < 0.01) with any dose of PCHE than that observed in the spontaneous recovery group. After the administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma, recovery of TOF ratio to 0.75 or more was observed in all patients in less than 10 min and time to attain a TOF ratio of 0.75 was 55% shorter than the spontaneous recovery group (8.4 [7.1-9.7] vs. 18.7 [15.4-22] min; mean and 95% confidence intervals).
CONCLUSIONS
Administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma (in a 65-kg patient, this dose is equivalent to PCHE activity of 1,625 ml of adult human plasma) resulted in reliable antagonism of mivacurium-induced neuromuscular blockade. Nevertheless, because of the prohibitive cost of this compound, this reversal modality is unlikely to have a routine practical application at this time.
Topics: Adolescent; Adult; Cholinesterases; Dose-Response Relationship, Drug; Female; Humans; Isoquinolines; Male; Middle Aged; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents
PubMed: 7574048
DOI: 10.1097/00000542-199510000-00008 -
Journal of Clinical Pathology Nov 1970A study has been made of the temperature activity relationships of the serum cholinesterase variants differentiated by means of dibucaine and fluoride inhibition. Using...
A study has been made of the temperature activity relationships of the serum cholinesterase variants differentiated by means of dibucaine and fluoride inhibition. Using benzoylcholine as substrate, there is a characteristic temperature activity curve for each phenotype, and, for those most sensitive to succinyldicholine, this differs radically from that of the normal enzyme.A true index of serum cholinesterase activity is obtained only at 37 degrees C, as at other temperatures various assumptions and correction factors have to be made, and the results could be misleading.
Topics: Apnea; Cholinesterase Inhibitors; Cholinesterases; Dibucaine; Fluorides; Humans; Phenotype; Succinylcholine; Temperature
PubMed: 5488048
DOI: 10.1136/jcp.23.8.730