ReN 1869, a novel tricyclic antihistamine, is active against neurogenic pain and inflammation》.pdf

European Journal of Pharmacology 435 (2002) 43– 57 /locate/ejphar ReN 1869, a novel tricyclic antihistamine, is active against neurogenic pain and inflammation a a a b Uffe B. Olsen , Christina T. Eltorp , Bente K. Ingvardsen , Tine K. Jørgensen , Jens A. Lundbæk a,c, Christian Thomsen d, Anker J. Hansen a,c,* aDepartment of General Pharmacology, Novo Nordisk A/S, 2760 Maaloev, Denmark bDepartment of Chemistry, Novo Nordisk A/S, 2760 Maaloev, Denmark cDepartment of Neuropharmacology, Novo Nordisk A/S, 2760 Maaloev, Denmark dDepartment of Molecular Pharmacology, Novo Nordisk A/S, 2760 Maaloev, Denmark Received 11 October 2001; received in revised form 19 November 2001; accepted 23 November 2001 Abstract The tricyclic compound (R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid (ReN 1869) is a novel, selective histamine H1 receptor antagonist. It is orally available, well tolerated, easily enters the central nervous system (CNS) but no adverse effects are seen in mice at 300 mg/kg. ReN 1869 at 0.01–10 mg/kg is antinociceptive in tests of chemical nociception in rodents (formalin, capsaicin, phenyl quinone writhing) but not in thermal tests (hot plate and tail flick). ReN 1869 amplifies the analgesic action of morphine but does not show tolerance after