caa a22 4500 469079533 CHVBK 20180323132946.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF00176624 doi (NATIONALLICENCE)springer-10.1007/BF00176624 Withdrawal precipitation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant β-carboline abecarnil [Elektronische Daten] [Wolfgang Löscher, Dagmar Hönack] Summary: The effects of the benzodiazepine (BZ) receptor antagonists flumazenil (Ro 15-1788) and the β-carboline ZK 93426 were compared in dogs before and after chronic treatment with diazepam or the novel BZ receptor ligand abecarnil (ZK 112119). Abecarnil, β-carboline, is thought to act as partial (low efficacy) and/or subtype selective agonist at central BZ receptors. Diazepam and abecarnil were administered at doses which, based on previous experiments on anticonvulsant activity, resulted in about equieffective drug concentrations during treatment. In dogs treated with diazepam, 6 mg/kg/day p.o., for 2 weeks, severe abstinence symptoms, including seizures, were precipitated in all animals by i. v. infusion of the BZ receptor antagonists, differences being found in the type of symptoms caused by flumazenil and ZK 93426. In dogs treated with abecarnil, 4 mg/kg/d s. c., for 6 weeks, only relatively mild abstinence symptoms were precipitated by infusion of flumazenil or ZK 93426, although pharmacologically active plasma concentrations of abecarnil had been maintained throughout the period of treatment. This suggests that BZ receptor ligands which act as partial and/or selective agonists might be more favourable than traditional agonists, such as diazepam, regarding the induction of physical dependence. Springer-Verlag, 1992 Benzodiazepines nationallicence \-Carbolines nationallicence Dependence nationallicence Tolerance nationallicence Flumazenil nationallicence Diazepam nationallicence Abecarnil nationallicence Precipitated withdrawal nationallicence Löscher Wolfgang Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, W-3000, Hannover 71, Germany aut Hönack Dagmar Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, W-3000, Hannover 71, Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 452-460 0028-1298 345:4<452 1992 345 210 https://doi.org/10.1007/BF00176624 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00176624 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Löscher Wolfgang Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, W-3000, Hannover 71, Germany aut NATIONALLICENCE 700 1- Hönack Dagmar Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, W-3000, Hannover 71, Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 452-460 0028-1298 345:4<452 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer