caa a22 4500 445853158 CHVBK 20180317145419.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00204-011-0719-9 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0719-9 In vivo assessment of antiemetic drugs and mechanism of lycorine-induced nausea and emesis [Elektronische Daten] [Sascha Kretzing, Getu Abraham, Bettina Seiwert, Fritz Ungemach, Ute Krügel, Jens Teichert, Ralf Regenthal] Lycorine is the main alkaloid of many Amaryllidaceae and known to cause poisoning with still unknown mechanisms. Longer lasting toxicological core symptoms of nausea and emesis may become a burden for human and animal patients and may result in substantial loss of water and electrolytes. To optimise the only empirical symptomatic antiemetic drug treatment at present, it is important to elucidate the causative involved targets of lycorine-induced emesis. Therefore, in the current study, we have tested the actions of a various antiemetic drugs with selective receptor affinities on lycorine-induced nausea and emesis in vivo in dogs. Beagle dogs were pre-treated in a saline vehicle-controlled crossover and random design with diphenhydramine, maropitant, metoclopramide, ondansetron or scopolamine prior lycorine administration (2mg/kgsubcutaneously). In vivo effects were assessed by a scoring system for nausea and emesis as well as by the number and lag time of emetic events for at least 3h. Moreover, plasma pharmacokinetic analysis was carried out for ondansetron before and after lycorine injection. The data show that histaminergic (H1), muscarinic and dopaminergic (D2) receptors are presumably not involved in lycorine-induced emetic effects. While ondansetron significantly reduced the number of emetic events, lycorine-induced emesis was completely blocked by maropitant. Only ondansetron also significantly decreased the level of nausea and was able to prolong the lag time until onset of emesis suggesting a preferential participation of 5-HT3 receptors in lycorine-induced nausea. Thus, it is the first in vivo report evidencing that predominantly neurokinin-1 (NK1) and to a lesser extent 5-hydroxytryptamine 3 (5-HT3) receptors are involved in lycorine-induced emesis facilitating a target-oriented therapy. Springer-Verlag, 2011 Lycorine nationallicence Alkaloid nationallicence Amaryllidaceae nationallicence Diphenhydramine nationallicence Maropitant nationallicence Metoclopramide nationallicence Ondansetron nationallicence Scopolamine nationallicence Toxicity nationallicence Mechanism nationallicence Emesis nationallicence Dogs nationallicence Kretzing Sascha Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut Abraham Getu Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut Seiwert Bettina Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut Ungemach Fritz Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut Krügel Ute Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany aut Teichert Jens Institute of Clinical Pharmacology, Faculty of Medicine, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany aut Regenthal Ralf Institute of Clinical Pharmacology, Faculty of Medicine, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany aut Archives of Toxicology Springer-Verlag 85/12(2011-12-01), 1565-1573 0340-5761 85:12<1565 2011 85 204 https://doi.org/10.1007/s00204-011-0719-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0719-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kretzing Sascha Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut NATIONALLICENCE 700 1- Abraham Getu Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut NATIONALLICENCE 700 1- Seiwert Bettina Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut NATIONALLICENCE 700 1- Ungemach Fritz Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany aut NATIONALLICENCE 700 1- Krügel Ute Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany aut NATIONALLICENCE 700 1- Teichert Jens Institute of Clinical Pharmacology, Faculty of Medicine, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany aut NATIONALLICENCE 700 1- Regenthal Ralf Institute of Clinical Pharmacology, Faculty of Medicine, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/12(2011-12-01), 1565-1573 0340-5761 85:12<1565 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer