1 Prof. Annamaria De Luca BREVE CURRICULUM VITAE Posizione

Prof. Annamaria De Luca BREVE CURRICULUM VITAE Posizione accademica: Professore Ordinario di Farmacologia Istituzione: Unità di Farmacologia, Dipartimento di Farmacia Università degli Studi di Bari “Aldo Moro” Carriera Accademica • 1985: Laurea "cum laude" in Farmacia presso la facoltà di Farmacia dell’Università degli Studi di Bari. • 1986: Stage di Ricerca post-­‐laurea presso il Department of Anatomy and Embryology, University College London, U.K. • 1987: Specializzazione "cum laude" in Farmacologia Applicata presso l’Università degli Studi di Bari. • 1989-­‐1991: Funzionario tecnico presso l’Unità di Farmacologia, Dipartimento Farmacobiologico, Facoltà di Farmacia, Università degli Studi di Bari • Settembre 1989-­‐Marzo 1990 : "Visiting scientist and professor" presso l’Istituto di Fisiologia Generale, Facoltà di Medicina, Università di Ulm (Germania). • 1991-­‐2000: Ricercatore di Farmacologia presso l’Unità di Farmacologia, Facoltà di Farmacia, Università degli Studi di Bari. • 2000-­‐2005: Professore Associato di Farmacologia, Facoltà di Farmacia, Università degli Studi di Bari. • Febbraio 2005-­‐oggi: Professore Ordinario di Farmacologia • Luglio 2013-­‐oggi: Coordinatore Consiglio dei Corsi di Classe LM-­‐13 (Farmacia e CTF), Università degli Studi di Bari Attività Didattica Dal 1991, la prof. De Luca ha avuto incarichi di insegnamento presso la Facoltà di Farmacia di Bari, indirizzati a studenti dei corsi di laurea magistrale a ciclo unico in Farmacia e Chimica e Tecnologie Farmaceutiche e dei corsi di laurea triennali in Informazione Scientifica sul Farmaco e Tecniche Erboristiche. Ha avuto inoltre incarichi d’isegnamento di discipline farmacologiche anche presso il Corso di Laurea in Biotecnologie della Facoltà di Scienze MM.FF.NN dell’Università di Lecce. In breve i corsi di insegnamento sono stati i seguenti: - Saggi e Dosaggi Farmacologici - Farmacologia Generale e Molecolare - Farmacologia e Farmacoterapia - Farmacologia e Tossicologia Svolge inoltre attività didattica post-­‐laurea: dottorato in “Scienze Biochimiche e Farmacologiche”, Scuola di Specializzazione in “Farmacia Ospedaliera”, Corso di Perfezionamento in “Farmacista di Reparto”, etc. Attività Scientifica Studi biofisici, biochimici e farmacologici mediante approcci multidisciplinari di miopatie ereditarie e di miopatie degenerative secondarie ad altre condizioni fisopatologiche. I principali campi di ricerca possono essere così riassunti: Distrofia Muscolare di Duchenne Canalopatie ereditarie del muscolo scheletrico (miotonie e paralisi) Miopatie da invecchiamento e disuso Miopatie da farmaci e tossici ambientali 1
FINANZAMENTI DI RICERCA Responsabile scientifico di progetti di ricerca e contratti conto terzi finanziati da: Telethon-­‐Italia, PRIN-­‐MIUR, Dutch Duchenne Parent Project (charity-­‐ Olanda), Scrass-­‐Group-­‐
Ipsen, France, Summit (UK), Galapagos (Francia), Servier (Francia) COMITATI SCIENTIFICI - Commissione Regionale per il Prontuario Terapeutico Ospedaliero; - Network di Eccellenza Europeo per lo studio delle Malattie Neuromuscolari (TREAT-­‐NMD) (http://www.treat-­‐nmd.eu/research/preclinical/SOPs/); - TREAT-­‐NMD Advisory Committee for Therapeutics (TACT) http://www.treat-­‐
nmd.eu/about/governance/TACT); - Comitato Scientifico della “Fondazione di Ricerca Farmacologica Gianni Benzi” (fino al 2011); http://www.benzifoundation.org/fondazione.php?p=5); ATTIVITA’ DI REVIEWER PER RIVISTE, SOCIETA’ E NETWORK SCIENTIFICI Editorial Board: Neuromuscular Disorder; Journal Neuromuscular Diseases Revisore: Human Molecular Genetics, American Journal of Pathology, Neurobiology of Disease, Molecular Therapy, Journal of Pharmacology and Experimental Therapeuticsm, Molecular Pharmacology, Neuropathology and Applied Neurobiology, Biochemical Pharmacology, American Journal Physiology (Cell Physiology), Journal Physiology (London), Journal of Applied Physiology, Journal of Neuroimmunology, Muscle Nerve. Attività di reviewer/consultant esterno: Association Françaises contre le Myopathies (AFM); Dutch Duchenne Parent Project (DPP/NL); WP 7.2 “Select appropriate animal models” Treat-­‐
NMD Neuromuscular Network; Medical Research Council (MRC), U.K.; Agence Nationale de la Recherche (ANR), France PRODUZIONE SCIENTIFICA Autore di più di 120 pubblicazioni in estenso su rivieste scientifiche indicizzate a comitato di lettura oltre a centinaia di abstract a congressi ELENCO PUBBLICAZIONI ULTIMI 10 ANNI (2000-­‐2014) 1.
Lynn S, Aartsma-­‐Rus A, Bushby K, Furlong P, Goemans N, De Luca A, Mayhew A, McDonald C, Mercuri E, Muntoni F, Pohlschmidt M, Verschuuren J, Voit T, Vroom E, Wells DJ, Straub V. Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy. Neuromuscul Disord. 2014 Sep 11. pii: S0960 8966(14)00637-­‐
3. doi: 10.1016/j.nmd.2014.09.003. [Epub ahead of print] 2.
Camerino GM, Cannone M, Giustino A, Massari AM, Capogrosso RF, Cozzoli A, De Luca A. Gene expression in mdx mouse muscle in relation to age and exercise: aberrant mechanical-­‐
metabolic coupling and implications for pre-­‐clinical studies in Duchenne muscular dystrophy. Hum Mol Genet. 23(21):5720-­‐32, 2014 3.
Cozzoli A, Liantonio A, Conte E, Cannone M, Massari AM, Giustino A, Scaramuzzi A, Pierno S, Mantuano P, Capogrosso RF, Camerino GM, De Luca A. Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase. Am J Physiol Cell Physiol. 307(7):C634-­‐
47, 2014 2
4.
De Bellis M., De Luca A, Desaphy J.F., Carbonara R., Heiny J.A., Kennedy A., Carocci A., Cavalluzzi M.M., Lentini G., Franchini C., Conte Camerino D. Combined Modifications of Mexiletine Pharmacophores for New Lead Blockers of Nav1.4 Channels. Biophys. J., vol. 104, p. 344-­‐354, 2013. 5.
Camerino GM, Bouchè M, De Bellis M, Cannone M, Liantonio A, Musaraj K, Romano R, Smeriglio P, Madaro L, Giustino A, De Luca A, Desaphy JF, Camerino DC, Pierno S. Protein kinase C theta (PKCθ) modulates the ClC-­‐1 chloride channel activity and skeletal muscle phenotype: a biophysical and gene expression study in mouse models lacking the PKCθ. Pflugers Arch. 466(12):2215-­‐28. 2014 6.
Pierno S, Tricarico D, Liantonio A, Mele A, Digennaro C, Rolland JF, Bianco G, Villanova L, Merendino A, Camerino Gm, De Luca A, Desaphy JF, Camerino DC. An olive oil-­‐derived antioxidant mixture ameliorates the age-­‐related decline of skeletal muscle function. Age (Dordr) 36(1):73-­‐88, 2014. 7.
Tamma R, Annese T, Capogrosso RF, Cozzoli A, Benagiano V, Sblendorio V, Ruggieri S, Crivellato E, Specchia G, Ribatti D, De Luca A, Nico B. Effects of prednisolone on the dystrophin-­‐associated proteins in the blood-­‐brain barrier and skeletal muscle of dystrophic mdx mice. Lab. Investig. vol. 93, p. 592-­‐610, 2013 8.
Cozzoli A, Capogrosso RF, Sblendorio VT, Dinardo MM, Jagerschmidt C, Namour F, Camerino GM, De Luca A. GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-­‐mdx mouse model of muscular dystrophy. Pharmacol. Res., vol. 72, p. 9-­‐24, 2013 9.
Pierno S, Camerino GM, Cannone M, Liantonio A, De Bellis M, Digennaro C, Gramegna G, De Luca A, Germinario E, Danieli-­‐Betto D, Betto R, Dobrowolny G, Rizzuto E, Musarò A, Desaphy JF, Camerino Dc. Paracrine Effects of IGF-­‐1 Overexpression on the Functional Decline Due to Skeletal Muscle Disuse: Molecular and Functional Evaluation in Hindlimb Unloaded MLC/mIgf-­‐1 Transgenic Mice. PLOS ONE, 8(6):e65167, 2013 10.
Willmann R, De Luca A, Benatar M, Grounds M, Dubach J, Raymackers JM, Nagaraju K. Enhancing translation: Guidelines for standard pre-­‐clinical experiments in mdx mice. Neuromuscul. Disord., vol. 22, p. 43-­‐49, 2012 11.
De Luca A . Pre-­‐clinical drug tests in the mdx mouse as a model of dystrophinopathies: an overview. Acta Myologica, vol. 31, p. 40-­‐47, 2012 12.
De Luca A, De Bellis M, Corbo F, Franchini C, Muraglia M, Catalano A, Carocci A, Conte Camerino D. Searching for novel anti-­‐myotonic agents: Pharmacophore requirement for use-­‐
dependent block of skeletal muscle sodium channels by N-­‐benzylated cyclic derivatives of tocainide. Neuromuscul. Disord., vol. 22, p. 56-­‐65, 2012 13.
Cozzoli A, Nico B, Sblendorio VT, Capogrosso RF, Dinardo MM, Longo V, Gagliardi S, Montagnani M, De Luca A. Enalapril treatment discloses an early role of angiotensin II in inflammation-­‐ and oxidative stress-­‐related muscle damage in dystrophic mdx mice. Pharmacol Res. 64(5):482-­‐92, 2011 14.
Cozzoli A, Rolland JF, Capogrosso RF, Sblendorio VT, Longo V, Simonetti S, Nico B, De Luca A. Evaluation of potential synergistic action of a combined treatment with alpha-­‐methyl-­‐
3
prednisolone and taurine on the mdx mouse model of Duchenne muscular dystrophy. Neuropathol. Appl. Neurobiol. 37(3): 243-­‐56, 2011 15.
Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, Powell DS, Cozzoli A, Capogrosso RF, Lambert A, Wilson FX, Wren SP, De Luca A, Davies KE. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One. 6(5):e19189, 2011 16.
Nico B, Tamma R, Annese T, Mangieri D, De Luca A, Corsi P, Benagiano V, Longo V, Crivellato E, Salmaggi A, Ribatti D. Glial dystrophin-­‐associated proteins, laminin and agrin, are downregulated in the brain of mdx mouse. Lab Invest. 90(11):1645-­‐60 2010. 17.
Burdi R, Rolland JF, Fraysse B, Litvinova K, Cozzoli A, Giannuzzi V, Liantonio A, Camerino GM, Sblendorio V, Capogrosso RF, Palmieri B, Andreetta F, Confalonieri P, De Benedictis L, Montagnani M, De Luca A. Multiple pathological events in exercised dystrophic mdx mice are targeted by pentoxifylline: outcome of a large array of in vivo and ex vivo tests. J. Appl. Physiol. 106(4):1311-­‐24, 2009. 18.
Nico B, Mangieri D, De Luca A, Corsi P, Benagiano V, Tamma R, Annese T, Longo V, Crivellato E, Ribatti D. Nerve growth factor and its receptors TrkA and p75 are upregulated in the brain of mdx dystrophic mouse. Neuroscience 161(4):1057-­‐66, 2009. 19.
Pierno S, Camerino GM, Cippone V, Rolland JF, Desaphy JF, De Luca A, Liantonio A, Bianco G, Kunic JD, George Jr AL, Conte Camerino D. Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-­‐1 channel regulation and expression. Br J Pharmacol. 156(8):1206-­‐15, 2009. 20.
De Luca A, Nico B, Rolland JF, Cozzoli A, Burdi R, Mangieri D, Giannuzzi V, Liantonio A, Cippone V, De Bellis M, Nicchia GP, Camerino GM, Frigeri A, Svelto M, Conte Camerino D. Gentamicin treatment in exercised mdx mice: identification of dystrophin-­‐sensitive pathways and evaluation of efficacy in work-­‐loaded dystrophic muscle. Neurobiol. Dis. 32(2):243-­‐53, 2008. 21.
Grounds MD, Radley HG, Lynch GS, Nagaraju K, De Luca A. Towards developing standard operating procedures for pre-­‐clinical testing in the mdx mouse model of Duchenne muscular dystrophy. Neurobiol. Dis. 31(1):1-­‐19, 2008. 22.
Pierno S, Desaphy JF, Liantonio A, De Luca A, Zarrilli A, Mastrofrancesco L, Procino G, Valenti G, Conte Camerino D. Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance. J Physiol. (Lond) 584: 983-­‐95, 2007. 23.
Pierno S, Nico B, Burdi R, Liantonio A, Didonna MP, Cippone V, Fraysse B, Rolland JF, Mangieri D, Andreetta F, Ferro P, Camerino C, Zallone A, Confalonieri P, De Luca A. Role of TNF-­‐alpha, but not of COX-­‐2 derived eicosanoids, on functional and morphological indices of dystrophic progression in mdx mice: a pharmacological approach. Neuropathol. Appl. Neurobiol. 33(3): 344-­‐59, 2007. 24.
Radley HG, De Luca A, Lynch GS, Grounds MD. Duchenne muscular dystrophy: Focus on pharmaceutical and nutritional interventions. Int J Biochem Cell Biol. 39(3):469-­‐77, 2007. 25.
Pierno S, Didonna MP, Cippone V, De Luca A, Pisoni M, Frigeri A, Nicchia GP, Svelto M, Chiesa G, Sirtori C, Scanziani E, Rizzo C, De Vito D, Conte Camerino D. Effects of chronic 4
treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study. Br J Pharmacol. 149(7):909-­‐19, 2006. 26.
Rolland JF*, De Luca A*, Burdi R, Andreetta F, Confalonieri P, Conte Camerino D. Overactivity of exercise-­‐sensitive cation channels and their impaired modulation by IGF-­‐1 in mdx native muscle fibers: Beneficial effect of pentoxifylline. (*equally contributing to the work). Neurobiol Dis. 24: 466-­‐474, 2006. 27.
De Bellis M*, De Luca A*, Rana F, Cavalluzzi MM, Catalano A, Lentini G, Franchini C, Tortorella V, Conte Camerino D. Evaluation of the pharmacological activity of the major mexiletine metabolites on skeletal muscle sodium currents. (*equally contributing to the work) Br J Pharmacol; 149(3): 300-­‐10, 2006. 28.
Fraysse B, Desaphy JF, Rolland JF, Pierno S, Liantonio A, Giannuzzi V, Camerino C, Didonna MP, Cocchi D, De Luca A, Conte Camerino D. Fiber type-­‐related changes in rat skeletal muscle calcium homeostasis during aging and restoration by growth hormone. Neurobiol Dis. 21(2):372-­‐80, 2006. 29.
Burdi R, Didonna MP, Pignol B, Nico B, Mangieri D, Rolland JF, Camerino C, Zallone A, Ferro P, Andreetta F, Confalonieri P, De Luca A. First evaluation of the potential effectiveness in muscular dystrophy of a novel chimeric compound, BN 82270, acting as calpain-­‐inhibitor and anti-­‐oxidant. Neuromuscul Disord. 16(4):237-­‐48, 2006. 30.
De Luca A, Nico B, Liantonio A, Didonna MP, Fraysse B, Pierno S, Burdi R, Mangieri D, Rolland JF, Camerino C, Zallone A, Confalonieri P, Andreetta F, Arnoldi E, Courdier-­‐Fruh I, Magyar JP, Frigeri A, Pisoni M, Svelto M, Conte Camerino D. A multidisciplinary evaluation of the effectiveness of cyclosporine A in dystrophic mdx mice. Am. J. Pathol. 166: 477-­‐489, 2005. 31.
Desaphy JF, Pierno S, Liantonio A, De Luca A, Didonna MP, Frigeri A, Nicchia GP, Svelto M, Camerino C, Zallone A, Conte Camerino D. Recovery of the soleus muscle after short-­‐ and long-­‐term disuse induced by hindlimb unloading: effects on the electrical properties and myosin heavy chain profile. Neurobiol Dis. 18: 356-­‐365, 2005. 32.
Desaphy JF, Didonna P, De Luca A, George AL Jr, Conte Camerino D. Different flecainide sensititivity of hNav1.4 channels and myotonic mutants explained by state-­‐dependent block. J. Physiol., (Lond) 554: 321-­‐334, 2004. 33.
De Luca A, Pierno S, Liantonio A, Desaphy JF, Natuzzi F, Didonna MP, Ferrannini E, Jockusch H, Franchini C, Lentini G, Corbo F, Tortorella V, Conte Camerino D. New potent mexiletine and tocainide analogues evaluated in vivo and in vitro as antimyotonic agents on the myotonic ADR mouse. Neuromuscul. Disord. 14: 405-­‐416, 2004. 34.
Fraysse B, Liantonio A, Cetrone M, Burdi R, Pierno S, Frigeri A, Pisoni M, Camerino C, De Luca A. The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo. Neurobiol. Dis. 17: 144-­‐154, 2004. 35.
Liantonio A, Pusch M, Picollo A, Guida P, De Luca A, Pierno S, Fracchiolla G, Loiodice F, Tortorella P, Conte Camerino D. Investigation of pharmacological properties of the renal CLC-­‐
K1 chloride channel co-­‐expressed with berttin by the use of 2-­‐(p-­‐chlorophenoxy)propionic acid derivatives and other structurally unrelated chloride channel blockers. J. Am. Soc. Nephrol., 15(1): 13-­‐20, 2004. 5
36.
Franchini C, Carocci A, Catalano A, Cavalluzzi MM, Corbo F, Lentini G, Scilimati A, Tortorella P, Conte Camerino D, De Luca A. Optically active mexiletine analogues as stereoselective blockers of voltage-­‐gated Na+ channels. J. Med. Chem. 46: 5238-­‐5248, 2003. 37.
De Luca A, Talon S, De Bellis M, Desaphy JF, Franchini C, Scilimati A, Lentini G, Corbo F, Tortorella V, Conte Camerino D. Optimal requirements for high affinity and use-­‐dependent block of skeletal muscle sodium channel by N-­‐benzyl analogs of tocainide-­‐like compounds. Mol. Pharmacol. 64(4): 932-­‐945, 2003. 38.
Pierno S, De Luca A, Desaphy JF, Liantonio A, Lograno M, Cocchi D, Smith RG, Conte Camerino D. Growth hormone secreatagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin-­‐specific receptor. Br. J. Pharmacol. 139: 575-­‐584, 2003. 39.
Fraysse B, Desaphy JF, Pierno S, De Luca A, Liantonio A, Mitolo CI, Conte Camerino D: Decrease in resting calcium and calcium entry associated with slow-­‐to-­‐fast transition in unloaded rat soleus muscle. FASEB J. 17: 1916-­‐1918, 2003. 40.
Liantonio A, De Luca A, Pierno S, Didonna P, Loiodice F, Fracchiolla G, Tortorella P, Laghezza A, Bonerba E, Traverso S, Elia L, Picollo A, Pusch M, Conte Camerino D. Structural requisites of 2-­‐(p-­‐chlorophgenoxy) propionic acid analogues for activity on native rat skeletal muscle chloride conductance and on heterologously expressed CLC-­‐1. Br. J. Pharmacol. 139(7):1255-­‐1264, 2003. 41.
De Luca A, Pierno S, Liantonio A, Cetrone M, Camerino C, Fraysse B, Mirabella M, Servidei S, Ruegg UT, Conte Camerino D. Enhanced dystrophic progression in mdx mice by exercise and beneficial effects of taurine and insulin-­‐like growth factor-­‐1. J. Pharmacol. Exp. Ther. 304: 453-­‐63, 2003. 42.
Desaphy JF, Pierno S, Didonna P, De Luca A, Didonna MP, Conte Camerino D. Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders. Mol. Pharmacol. 63:659-­‐670, 2003. 43.
De Luca A*, Talon S*, De Bellis M, Desaphy JF, Franchini C, Lentini G, Catalano A, Corbo F, Tortorella V, Conte Camerino D. Inhibition of skeletal muscle sodium currents by mexiletine analogues: specific hydrophobic interactions rather than lipophilia per se account for drug therapeutic profile (*equally contributing to the work). N.S. Archiv Pharmacol. 367: 318-­‐327, 2003. 44.
Liantonio A, Accardi A, Carbonara G, Fracchiolla G, Loiodice F, Tortorella P, Traverso S, Guida P, Pierno S, De Luca A, Conte Camerino D, Pusch M. Molecular requisites for drug binding to muscle CLC-­‐1 and renal CLC-­‐K channel revealed by the use of phenoxy-­‐alkyl derivatives of 2-­‐(p-­‐chlorophenoxy)propionic acid. Mol. Pharmacol. 62:265-­‐71, 2002. 45.
Pierno S, Desaphy JF, Liantonio A, Frigeri A, Nicchia GP, Svelto M, Bianco G, Léoty C, George AL, De Luca A, Conte Camerino D. Change of chloride ion channel conductance is an early event of slow-­‐to-­‐fast fibre type transition during unloading-­‐induced muscle disuse. Brain 125:1510-­‐21, 2002. 6
46.
Desaphy JF, De Luca A, Tortorella V, De Vito D, George AL, Conte Camerino D. Gating of myotonic Na channel mutants defines the response to mexiletine and a potent derivative. Neurology 57: 1849-­‐1856, 2001. 47.
Talon S*, De Luca A*, De Bellis M, Desaphy JF, Lentini G, Scilimati A, Corbo F, Franchini C, Tortorella V, Jockusch H, Conte Camerino D. Increased rigidity of the chiral centre of tocainide favours stereoselectivity and use-­‐dependent block of skeletal muscle Na+ channels enhancing the antimyotonic activity in vivo (*equally contributing to the work). Br. J. Pharmacol. 134: 1523-­‐1531, 2001. 48.
Frigeri A, Nicchia P, Desaphy JF, Pierno S, De Luca A, Conte Camerino D, Svelto M. Muscle loading modulates aquaporin-­‐4 expression in skeletal muscle. FASEB J. 15: 1282-­‐1284, 2001. 49.
Pusch M, Accardi A, Ferrera L, Liantonio A, De Luca A, Conte Camerino D, Conti F. Mechanism of block of single protopores of the Torpedo chloride channel ClC-­‐0 by 2-­‐(p-­‐
chlorophenoxy)butyric acid (CPB). J. Gen. Physiol. 118: 45-­‐62, 2001. 50.
De Luca A, Pierno S, Liantonio A, Cetrone M, Camerino C, Simonetti S, Papadia F, Conte Camerino D. Alteration of excitation-­‐contraction coupling mechanism in extensor digitorum longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine. Br. J. Pharmacol. 132: 1047-­‐1054, 2001. 51.
Desaphy JF, Pierno S, Leoty C, George AL, De Luca A, Conte Camerino D. Skeletal muscle disuse fiber type-­‐dependent enhancement of Na+ channel expression. Brain, 124: 1100-­‐1113, 2001. 52.
Pusch M, Liantonio A, Bertorello L, Accardi A, De Luca A, Pierno S, Tortorella V, Conte Camerino D. Pharmacological characterization of chloride channels belonging to the ClC family by the use of chiral clofibric acid derivatives. Mol. Pharmacol. 58: 498-­‐507, 2000. 53.
Franchini C, Corbo F, Lentini G, Bruno G, Scilimati A, Tortorella V, Conte Camerino D, De Luca A. Synthesis of new 2,6-­‐prolylxylidide analogues of tocainide as stereoselective blockers of voltage gated Na+ channel with increased potency and improved use-­‐dependent activity. J. Med. Chem. 43: 3792-­‐3798, 2000. 54.
Conte Camerino D, Pierno S, De Luca A, Bryant SH. Antimyotonic effects of tocainide enantiomers on skeletal muscle fibers of congenitally myotonic goats. Neuromuscul. Disord. 10: 160-­‐164, 2000. 55.
De Luca A, Natuzzi F, Desaphy JF, Loni G, Lentini G, Franchini C, Tortorella V, Conte Camerino D. Molecular determinants of mexiletine structure for potent and use-­‐dependent block of skeletal muscle sodium channels. Mol. Pharmacol. 57: 268-­‐277, 2000. 7