Protocol: [H]-Girisopam, a novel selective benzodiazepine for the 2,3-benzodiazepine binding site

Several members of the 2,3-benzodiazepine family, such as tofisopam (Grandaxin(r)) nerisopam (GYKI-52 322) [F. Andrasi, K. Horvath, E. Sineger, P. Berzsenyi, J. Borsy, A. Kenessey, M. Tarr, T. Lang, J. K rosi, T. Hamori, Neuropharmacology of a new psychotropic 2,3-benzodiazepine, Arzneim.-Forsch. Drug. Res., 37 (1987) 1119-1124.] [1] or girisopam (GYKI-51 189) [K. Horvath, F. Andrasi, P. Berzsenyi, M. Patfalusi, M. Patthy, G. Szabo, L. Sebestyen, J. K rosi, P. Botka, T. Hamori, T. Lang, A new psychoactive 5H-2,3-benzodiazepine with a unique spectrum of activity, Arzneim.-Forsch. Drug. Res., 39 (1989) 894-899.] [2] proved anxiolytic in man and various animal models. Moreover, girisopam could also be characterized as an atypical neuroleptic agent. In spite of the structural similarity, their pharmacological profiles differ significantly from that of the 'classical' 1,4-benzodiazepines. Importantly, according to the data obtained so far these drugs do not have an addiction potential. The novel 2,3-benzodiazepine antagonist girisopam binds with high affinity (Kd=10.3±1.21 nM) and limited capacity (Bmax=6.94±1.8 pmol/mg protein) to a single class of recognition sites in rat striatum [J.E. Horvath, J. Hudak, M. Palkovits, Zs. Lenkei, M.I.K. Fekete, P. Aranyi, A novel specific binding site for homophthalazines (formerly 2,3-benzodiazepines) in the rat brain, Eur. J. Pharmacol., 236 (1993) 151-153.]. This protocol describes the use of [3H]-girisopam as a specific radioligand for the 2,3-benzodiazepines receptor.Themes: Neurotransmitters, modulators, transporters and receptors.Topics: Regional localization of receptors and transmitters, biochemical characterization.