Efecto de la dibucaína sobre la SERCA del músculo pterigoideo interno / Drug action of dibucaine on the SERCA from medial pterygoid muscle

Objetivo: Determinar el efecto del anestésico local di-bucaína sobre las principales isoformas de la SERCA (calcio ATPasa de retículo sarco-endoplásmico) pre-sentes en músculo pterigoideo interno. Métodos: Se aislaron por centrifugación diferencial membranas de retículo sarcoplásmico de pterigoideo interno de conejo neozelandés macho (n=5). Se separaron las isoformas SERCA1a, 2a y 2b por cromatografía de afinidad. Se determinó in vitro la actividad enzimá-tica en presencia de diferentes concentraciones de dibucaína (0-90 mM) por el método de Fiske y Subba-row, realizando 5 experimentos por duplicado y en paralelo para cada isoforma. Se calculó la media y ES de la CI50 (mM) del anestésico para cada isofor-ma y éstas se compararon por ANOVA de una vía (p<0,05), y prueba Student-Newman-Keuls de com-paraciones múltiples. Resultados: Dibucaína inhibió la actividad enzimática en función de su concentra-ción en las tres isoformas en estudio. Las CI50 fueron: SERCA1a 20,02 ± 0,64 mM, SERCA2a 15,03 ± 0,52 mM y SERCA2b 16,00 ± 0,51 mM y resultaron signi-ficativamente diferentes (F2,27 = 11,08, p<0,001). La prueba post hoc identificó diferencias significativas entre SERCA1a y 2a, 1a y 2b. El efecto inhibitorio re-sultó significativamente mayor sobre las isoformas 2a y 2b, cuya presencia es sustancialmente mayor en músculos masticadores. Conclusión: La dibucaína inhibe a la SERCA de pterigoideo interno a concen-traciones menores que las usadas en clínica médica (29 mM). Es un anestésico local con potencial efecto miotóxico derivado de la inhibición de la SERCA (AU)

Aim: To test the effect of the local anesthetic dibu-caine on the main isoforms of the SERCA (sarco-endosplasmic reticulum calcium-ATPase) in medial pterygoid muscle. Methods: Sarcoplasmic reticulum membranes from male New Zealand rabbits (n=5) were isolated from medial pterygoid muscle by ul-tracentrifugation. The isoforms SERCA1a, 2a and 2b were separated using high affinity chromatography. In vitro enzymatic activity determinations were per-formed in the presence of different dibucaine con-centrations (0-90 mM) using the colorimetric method described by Fiske & Subbarow. Five assays in dupli-cate and run in parallel were performed for each of the isoforms. Mean and SEM of the IC50 (mM) for the effect of the anesthetic on each isoform were calcu-lated and compared by one-way ANOVA (p<0.05), and Student-Newman-Keuls multiple comparisons test. Results: Dibucaine inhibited the enzymatic activity in a concentration-dependent manner for the three studied isoforms. The IC50 values were: SERCA1a 20.02 ± 0.64 mM, SERCA2a 15.03 ± 0.52 mM and SER-CA2b 16.00 ± 0.51 mM. The values were significantly different (F2.27 = 11.08, p<0.001). The post hoc test revealed significant differences between SERCA1a and 2a, 1a and 2b. The inhibitory effect was signifi-cantly higher on 2a and 2b isoforms, whose presence is substantially higher in masticatory muscles. Con-clusion: Dibucaine inhibits SERCA in medial pterygoid muscle at concentrations lower than those used in clinical medicine (29 mM). It is a potentially myotoxic local anesthetic whose toxic effect may derive from SERCA inhibition (AU)

Allergic Contact Dermatitis due to a Topical Antipruritic Containing Dibucaine / 대한피부과학회지

Dibucaine hydrochloride is an amide-type local anesthetic and it is well known to be a contact allergen. Although there are some reports of allergic contact dermatitis due to over-the-counter medications containing dibucaine in the foreign literature, there is only one report of it in the Korean literature. We report here on a case of allergic contact dermatitis due to an over-the-counter drug containing dibucaine in a 41-year-old-woman. The patch test with the preparation that she had used and the TRUE(R) test revealed positive reactions to the dibucaine mix and Moscool(R).

Roles of Na+-Ca2+ exchange in the negative force-frequency relationship

Frequency-force relationships (FFR) were studied in electrically field stimulated rat left atria (LA) by reducing the stimulation frequency from resting 3 Hz to test frequencies (0.1-1 Hz) for 5 minutes. The twitch amplitudes of LA elicited the typical negative staircases with 3-phased changes: the initial rapid increase, the second decrease and the following plateau at test frequencies. Verapamil (3 X 10-5 M) pretreatment elicited frequency-dependent suppression of the twitch amplitudes, exaggerating the negative staircase. Monensin pretreatment enhanced not the peak but the plateau amplitudes in a concentration-dependent manner. When the Na+-Ca2+ exchange was blocked by Na+ and Ca2+ depletion in the Krebs Hensleit buffer (0 Na+-0 Ca2+ KHB), the twitch amplitudes increased in a frequency-dependent manner, changing the negtive staircase into the positve one. Meanwhile, the 0 Na+-0 Ca2+ KHB applicationinduced enhancement was strongly suppressed by caffeine (5 mM) pretreatment. Only dibucaine among the local anesthetics increased the basal tone during frequency reduciton. There were no differences in 45Ca uptakes between 0.3 Hz and 3 Hz stimulation except at 1 min when it was significantly low at 0.3 Hz than 3 Hz, illustrating net Ca2+ losses. Monensin pretreatment enhanced the rate of this Ca2+ loss. Taken together, it is concluded that Na+-Ca2+ exchange extrudes more SR released Ca2+ out of the cell in proportion to the frequency, resulting in the negative rate staircase in the rat LA.

Inhibition Numbers of Pseudocholinesterase in Korean Adults / 대한마취과학회지

Pseudocholinesterase is an essential enzyme for hydrolysis of succinylcholine and some people has low activity. The pseudocholinesterase from a normal individual has a greater apparent affinity for the cholinester substrate than the enzyme from succinylcholine-sensitive individuals, who has genetic variants. The ideal situation would be one in which a single, simple test would detect and identify all the variant forms of enzyme, but no such test currently exsits. The inhibitors frequently used to identify variants are dibucaine, fluoride, chloride, urea or succinylcholine as inhibition numbers. The authors found that dibucaine, fluoride and chloride numbers in Korean adults (mean+/-SD, %) are 85.8+/-1.83, 46.5+/-2,05 and 3.53+/-1.64, respectively (substrate is butyrylthiocholine).

Prolonged Neuromuscular Blockade Following Succinycholine Administration in a Patient with Plasma Cholinestrase Variant / 대한마취과학회지

The authors experienced a case of plasma cholinesterase variant who received succinylcholine, atracurium and reversal with pyridostigmine, and showed prolonged neuromuscular blockade postoperatively, and was ventilated artificia1ly until complete recovery. The patient and her two children later gave samples of blood. The patients blood revealed very low plasma cholinesterase activity of 0.11 IU/L(normal range; 5-12 IU/L) and dibucaine number of 33. In consideration of her childrens plasma cholinesterase activities and dibucaine numbers, we suggest that she has genetically abnormal plasma cholinesterase and probably her genotype is E E or E E.

A Clinical Study of T-cain and Dibucaine in Spinal Anesthesia / 대한마취과학회지

T-can is one of the most widely available local anesthetics for spinal anesthesia in Korea and we use T-cain almost exclusively. However, some anesthetists prefer other local anesthetics such as dibucaine, bupivacaine, or lidocaine for spinal anesthesia. We examined the hemodynamic effects, onset, spread, and duration of sensory and motor blockade following spinal anesthesia with 0.5% T-cain, 0.24% dibucaine, and 0.3% dibucaine. The results were as follows: 1) The blood pressure and pulse rate were decreased by all three drugs without significant difference among the three drugs. 2) The onset of sensory blockade was faster with T-cain than with dibucaine. T-cain containing 0.24% dibucaine had faster onset than the 0.3% solution. The spread of analgesia was also more rapid with T-cain than with dibucaine. 3) The motor blockade was significantly faster and more profound with T-cain than with dibucaine. 4) The duration of anesthesia was the shortest with T-cain containing 0.24% dibucaine and the longest with 0.3% dibucaine, but there was no statistical significance. From the above results, T-cain proved to be a more profound and shorter lasting local anesthetic than dibucaine. However, sensory and motor blockade produced by dibucaine were clinically acceptable. Therefore, both T-cain and dibucaine can be clinically available for spinal anesthesia.