PPDF ICB - UFRJ
Muscle Excitation -contraction of Pharmacology Laboratory



Summary of the 5 most relevant articles in the group

NELSON TE, LIN M, ZAPATA-SUDO G, SUDO RT. Dantrolene sodium can increase or attenuate activity of skeletal muscle ryanodine receptor calcium release channel: clinical implications. Anesthesiology (Philadelphia). , v.84, p.1368 - 1379, 1996.

Summary: The article describes for the first time that dantrolene sodium , only effective substance for the treatment of malignant hyperthermia interacts at two sites of action in the channel / recepotor ryanodine , in the regulation of Ca2 + release from the sarcoplasmic reticulum to mioplasma . Using the isolated preparation of bare fibers it was demonstrated that inhibition of release occurs in micromolar concentration ( low affinity ) but at nanomolar concentration ( high affinity ) sodium dantrolene unlike its beneficial effect , increases the release of Ca 2+ . It was suggested that this action is linked with the recrudescence of hyperthermia crisis with dantrolene sodium treatment period.

SUDO RT, ZAPATA-SUDO G, BARREIRO EJ. The new compound, LASSBio294, increases the contractility of intact and saponin-skinned cardiac muscle from Wistar rats. British Journal of Pharmacology. , v.134, p.603 - 613, 2001.
Summary: The article describes cardiac inotropic activity of the new compound 3,4- metilenedioxibenzoil -2- tienilhidrazona designated LASSBio -294 with potential application for the treatment of congestive heart failure. Initial experiments were performed in isolated rat hearts. In preparing permeabilized ventricular cells with saponin was shown that LASSBio -294 's action results in greater accumulation of Ca2 + into the sarcoplasmic reticulol . In in vivo experiments it was characterized reduced cardiotoxicity differing from cardiac glycoside , classic positive inotropic .


TRACHEZ MM, ZAPATA-SUDO G, MOREIRA OR, CHEDID NGB, RUSSO VFT, RUSSO EMS, SUDO RT.Motor nerve blockade potency and toxicity of non-racemic bupivacaine in rats. Acta Anaesthesiologica Scandinavia. , v.49, p.66 - 71, 2005.

Summary: Bupivacaine racemic (RS ( ± ) -bupivacaine ) is the local anesthetic greater clinical use. Its clinical use has been associated with severe cardiotoxicity. The S isomer ( -) - bupivacaine is known as being less toxic , but less power . This work shows for the first time evaluation of potency and toxicity of a non - racemic mixture consisting of 75S (-): 25R (+ ) - bupivacaine. This new mixture reduced the cardiotoxidade the racemic mixture and maintained its power . The development work has been targeted non- racemic mixture of bupivacaine for use in therapy . Brazil is pioneering this innovation and the product is in clinical use.


SUDO RT, CARMO PL, TRACHEZ MM, ZAPATA-SUDO G. Effects of azumolene on normal and malignant hyperthermia susceptible skeletal muscle. Basic & Clinical Pharmacology & Toxicology. , v.102, p.308 - 316, 2008.
Summary: The aim of this study was to evaluate the power of sodium azumolene , analogue of dantrolene sodium 30 times more hidrosssolúvel . The study was conducted : 1 ) skeletal muscle isolated from mice (in vitro study) ; 2 ) gastrocnemius muscle of guinea pigs (in vivo) ; 3 ) human vastus lateralis muscle fragments from normal patients and patients with malignant hyperthermia (MH ) . The results showed that the power was equal to azumolene sodium dantrolene experiments both in vitro and in vivo in muscles of mice and guinea pigs , respectively. Azumolene ( 10 uM ) was effective in the prevention and reversal of the contraction induced muscle caffeine fragment taken from a patient with HM . This work suggests the development of azumolene in view of clinical use for treatment of HM replacing the poorly soluble prototype, dantrolene sodium.

SUDO RT, Cunha LBP, CARMO PL, MATOS AR, TRACHEZ MM, CARDOSO ALM, AGUIAR MIS, ABREU AV, ZAPATA-SUDO G. Use of the caffeine-halothane contracture for malignant hyperthermia diagnosis in Brazil. Brazilian Journal of Medical and Biological Research (Impresso). , v.43, p.549 - 556, 2010
Summary: This paper shows the result of hyperthermia Diagnostic Center Malignant incubated in Drug Development Research Program ICB / UFRJ during the period 1993 to 2010. This national reference center provides the basis for the Brazilian Society of Anesthesiology . The model used by this center was the same as approved by the Association of Malignant Hyperthermia in North America which measures the vastus lateralis muscle biopsy contracture in response to exposure to halothane and caffeine . Most patients came from the Southeast (N = 110 ) and south (N = 71 ) of the country , the average age was 25 years and made ??up of 104 men and 90 women . The examination was performed in 194 and susceptibility to HM was identified in 90 patients .

SUDO RT, CALAZANS-MAIA JA, GALDINO SL, LIMA MCA, ZAPATA-SUDO G, HERNANDES MZ, PITTA IR. Interaction of morphine with a new alfa2-adrenoceptor agonist in mice. Journal of Pain. , v.11, p.71 - 78, 2010.
Summary: The discovery of the analgesic activity of new compounds acting on the central nervous system is clinically relevant. This work shows the analgesic activity of an analogous compound of 3-benzyl- imidazolidine (PT- 31) searched in hot plate model in mice. Isobolográfico study showed synergistic interaction of the PT -31 with morphine . Through the use of specific antagonists was characterized that the action of the PT -31 results from alpha- 2A adrenergic receptor activation , which was corroborated by docking studies. The PT- 31 is potentially important substance as centrally acting analgesic use may be enhanced by morphine.


 

 


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