Indantadol

Jiří Patočka

     Indantadol (N-(2,3-dihydro-1H-inden-2-yl)glycinamid, CHF-3381, V-3381, CAS Number 202844-10-8) je synteticky připravená látka, která byla nejdříve zkoušena jako antikonvulzivum s antiepileptogenním účinkem (Villeti et al., 2001) a neuroprotektivum (Gandolfi et al., 2001; Zucchini et al., 2002), ale v současné době je o ni uvažováno jako o možném léčivu neuropatické bolesti (Villetti et al., 2003; Astruc  et al., 2005; Bassani  et al., 2005; Mattia a Coluzzi, 2007) a jako o léku na chronický kašel (Brew a Bannister, 2012, 2014).

      Indantadol působí jako kompetitivní a reverzibilní inhibitor monoaminoxidázy a nekompetitivní antagonista NMDA-receptorů s nízkou afinitou (Csajka et al., 2005; Mathiesen et al., 2006). V současné době je indantadol ve fázi klinického zkoušení jako lék proti chronickému kašli (Vernalis, 2009a) a jako lék na neuropatickou bolest (Vernalis, 2009b).

Literatura
Astruc B, Tarral A, Dostert P, Mariotti F, Fabbri L, Imbimbo BP. Steady-state  pharmacokinetics and pharmacodynamics of CHF3381, a novel antineuropathic pain agent, in healthy subjects. Br J Clin Pharmacol. 2005; 59(4): 405-414.
Bassani F, Bergamaschi M, Tonino Bolzoni P, Villetti G. CHF3381, a novel antinociceptive agent, attenuates capsaicin-induced pain in rats. Eur J Pharmacol. 2005; 519(3): 231-236.
Brew J, Bannister RM. U.S. Patent Application 13/446,217, 2012.
Brew J, Bannister RM. U.S. Patent Application 14/287,014, 2014.
Csajka C, Imbimbo BP, Piccinno A, Dostert P, Verotta D. Mechanistic pharmacokinetic and pharmacodynamic modeling of CHF3381 (2-[(2,3-dihydro-1H-inden-2-yl)amino]acetamide monohydrochloride), a novel N-methyl-D-aspartate antagonist and monoamine oxidase-A inhibitor in healthy subjects. J Pharmacol Exp Ther. 2005; 313(2): 647-657.
Gandolfi O, Bonfante V, Voltattorni M, Dall'Olio R, Poli A, Pietra C, Villetti G. Anticonvulsant preclinical profile of CHF 3381: dopaminergic and glutamatergic mechanisms. Pharmacol Biochem Behav. 2001; 70(1): 157-166.
Mathiesen O, Imbimbo BP, Hilsted KL, Fabbri L, Dahl JB. CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model. J Pain. 2006; 7(8): 565-574.
Mattia C, Coluzzi F. Indantadol, a novel NMDA antagonist and nonselective MAO  inhibitor for the potential treatment of neuropathic pain. IDrugs. 2007; 10(9): 636-644.
Vernalis (R & D) Limited. Phase II Open-label Pilot Study of V3381, a Novel N-Methyl-D-Aspartate Receptor Antagonist, in Chronic Cough Patients attending a Specialist Clinic. 2009a.
Vernalis (R & D) Limited. A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Parallel Group Study of the Safety, Tolerability and Efficacy of V3381 for Up to 13 Weeks in Patients with Diabetic Peripheral Neuropathy. 2009b.
Villetti G, Bergamaschi M, Bassani F, Bolzoni PT, Maiorino M, Pietra C, Rondelli I, Chamiot-Clerc P, Simonato M, Barbieri M. Antinociceptive activity of  the N-methyl-D-aspartate receptor antagonist N-(2-Indanyl)-glycinamide hydrochloride (CHF3381) in experimental models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2003; 306(2): 804-814.
Villetti G, Bregola G, Bassani F, Bergamaschi M, Rondelli I, Pietra C, Simonato M. Preclinical evaluation of CHF3381 as a novel antiepileptic agent. Neuropharmacology. 2001; 40(7): 866-878.
Zucchini S, Buzzi A, Bergamaschi M, Pietra C, Villetti G, Simonato M. Neuroprotective activity of CHF3381, a putative N-methyl-D-aspartate receptor antagonist. Neuroreport. 2002; 13(16): 2071-2074.