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Emesis

Endo, T., M. Minami, M. Hirafuji, N. Hamaue, and S.H. Parvez (2004). The ferret: A cytotoxic drug-induced emesis model. Biogenic Amines 18(3-6): 419-434. ISSN: 0168-8561.
Descriptors: ferret, animal model, emesis, Mustela, cytotoxic drugs, vagus nerve, emetic stimuli, Cisplatin induced, vagotomy.

Kan, K.K., R.L. Jones, M.P. Ngan, and J.A. Rudd (2002). Actions of prostanoids to induce emesis and defecation in the ferret. European Journal of Pharmacology 453(2-3): 299-308. ISSN: 0014-2999.
Abstract: Several prostanoids were investigated for their ability to induce emesis and/or defecation and tenesmus in the ferret. The rank order of emetic potency (dose producing four episodes, D4) was: sulprostone (5 microg/kg)>11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619; 8 microg/kg)>misoprostol (27 microg/kg)>17-phenyl-omega-trinor prostaglandin E2 (53 microg/kg)>prostaglandin E2 (94 microg/kg)>5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C; 148 microg/kg)>>prostaglandin F(2alpha) (13,500 microg/kg). Emesis was also induced by iloprost (D4 not determined) and prostaglandin E2 methyl ester (D4=350 microg/kg). Cicaprost and fluprostenol were virtually inactive; they also failed to modify copper sulphate (100 mg/kg, intragastric)-induced emesis (P>0.05), although cicaprost potentiated apomorphine (0.25 mg/kg, s.c.)-induced emesis (P<0.05). U46619-induced emesis was antagonised by vapiprost (P<0.05). The rank order of potency to produce defecation and tenesmus (dose producing three episodes) was: sulprostone (12 microg/kg)>misoprostol (15 microg/kg)>17-phenyl-omega-trinor prostaglandin E2 (94 microg/kg)>prostaglandin E2 (113 microg/kg)>fluprostenol (158 microg/kg)z.Gt;prostaglandin F(2alpha) (1759 microg/kg); prostaglandin E2 methyl ester also induced defecation (196 microg/kg). Data are discussed in relation to mechanisms involved in emesis and defecation.
Descriptors: ferrets, defecation, prostaglandins, chemically induced vomiting, dose response relationship.

Kan, K.K., J.A. Rudd, and M.K. Wai (2006). Differential action of anti-emetic drugs on defecation and emesis induced by prostaglandin E2 in the ferret. European Journal of Pharmacology 544(1-3): 153-159. ISSN: 0014-2999.
Abstract: In the present studies we investigated the mechanism of action of prostaglandin E2 (1 mg/kg, i.p.) to induce emesis and defecation and/or tenesmus in the ferret. The emesis was antagonized significantly (P<0.05) by ondansetron (0.3 and 1 mg/kg, i.p.) and (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenlypiperidine hydrochloride (CP-99,994; 10 mg/kg, i.p.), but neither compound reduced defecations and/or tenesmus, with ondansetron (0.3 mg/kg) actually producing a slight increase (P<0.05). Droperidol (1 and 3 mg/kg), metoclopramide (0.3 and 3 mg/kg), domperidone (0.3 and 3 mg/kg), promethazine (0.3 and 3 mg/kg) and scopolamine (0.3 and 3 mg/kg) failed to reduce prostaglandin E2 induced emesis. However, droperidol (1 and 3 mg/kg) and scopolamine (0.3 and 3 mg/kg) reduced significantly the defecatory and/or tenesmus response (P<0.05). Bilateral abdominal vagotomy was ineffective to reduce emesis and defecations and/or tenesmus. The data suggests that 5-HT3 receptor and NK1 tachykinin receptor antagonists could be useful in the clinic to prevent emesis but not defecations induced by prostaglandin E2.
Descriptors: ferret, anti-emetic drugs, prostaglandin E2, emesis, defecations, tenesmus.

King, A.G. and G.J. Sanger (2005). Effect of a selective and potent central nervous system penetrant, neurokinin-3 receptor antagonist (SB-222200), on cisplatin-induced emesis in the ferret. Neuroscience Letters 376(1): 5-8. ISSN: 0304-3940.
Abstract: The anti-emetic activity of selective NK-1 receptor antagonism is well established. However, little is known of the possibility that other NK receptors might also be involved in the emetic reflex. Given the reported location of NK-3 receptors within the rat brainstem vagal motor and sensory nuclei, we investigated the ability of SB-222200, a brain-penetrant NK-3 receptor antagonist, to interfere with emesis evoked in ferrets by the emetogenic cytotoxic agent cisplatin. In contrast to control anti-emetic experiments using the 5-HT3 receptor antagonist ondansetron, SB-222200 was found to have no effects on cisplatin-induced vomiting or on the associated reductions in feeding and drinking behaviors at any dose tested. We suggest that if NK-3 receptors are involved in the mechanisms of cisplatin-induced nausea and vomiting, they play only a minor role, relative to the major anti-emetic activity exhibited by 5-HT3 or NK-1 receptor antagonism.
Descriptors: ferrets, therapeutic use of antiemetics, quinolines, vomiting, drug therapy, behavior, carrier proteins, cisplatin, dose response relationship, drug interactions.

Lao, L., G. Zhang, R.H. Wong, A.K. Carter, R.L. Wynn, and B.M. Berman (2003). The effect of electroacupuncture as an adjunct on cyclophosphamide-induced emesis in ferrets. Pharmacology, Biochemistry, and Behavior 74(3): 691-699. ISSN: 0091-3057.
Abstract: The effect of electroacupuncture (EA) on cyclophosphamide-induced emesis in ferrets was studied at acupuncture point Neiguan (P6) with various electrical stimulation parameters (5-100 Hz, 1.5-3 V, 5-20 min, n=6/group). The combination therapy of EA (100 Hz, 1.5 V and 10 min) with the lower doses of ondansetron (0.04 mg/kg), droperidol (0.25 mg/kg) and metoclopramide (2.24 mg/kg) significantly reduced the total number of emetic episodes by 52%, 36% and 73%, respectively, as well as the number of emetic episodes in the first phase as compared to the sham acupuncture control (P<.01). These EA/drug combinations also showed a significant effect in preventing emesis as compared to either EA or drug alone (P<.05). The present study suggests that acupuncture may be useful as an adjunctive therapy in the treatment of chemotherapy-induced emesis.
Descriptors: ferrets, induced emesis, electroacupuncture, vomiting, antiemetics, combined modality therapy methods.

Lau, A.H., K.K. Kan, H.W. Lai, M.P. Ngan, J.A. Rudd, M.K. Wai, and D.T. Yew (2005). Action of ondansetron and CP-99,994 to modify behavior and antagonize cisplatin-induced emesis in the ferret. European Journal of Pharmacology 506(3): 241-247. ISSN: 0014-2999.
Abstract: The action of ondansetron (1 mg/kg, i.p.) and (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994; 10 mg/kg, i.p.) on spontaneous behavior and the emesis induced by cisplatin (10 mg/kg, i.p.) was studied in the ferret. Ondansetron was inactive to modify behavior, but CP-99,994 reduced spontaneous locomotor activity and lip licking by 48% (P<0.01) and 79% (P<0.01), respectively; CP-99,994 also abolished spontaneous burrowing activity (P<0.05). Treatment of animals with cisplatin induced an emetic response that was abolished by both ondansetron and CP-99,994 (P<0.01). However, cisplatin did not significantly modify other behavioral measures although animals that received CP-99,994, cisplatin, or CP-99,994 in combination with cisplatin exhibited more episodes of defecation than animals that received ondansetron (P<0.05). The action of CP-99,994 to modify behavior in this species is discussed in relation to animal models of nausea.
Descriptors: ferrets, behavior, cisplatin antagonists, ondansetron, piperidines, vomiting, therapeutic use of antiemetics, animal physiology.

Lau, A.H., M.P. Ngan, J.A. Rudd, and D.T. Yew (2005). Differential action of domperidone to modify emesis and behaviour induced by apomorphine in the ferret. European Journal of Pharmacology 516(3): 247-252. ISSN: 0014-2999.
Abstract: The action of domperidone (1 mg/kg, i.p.) on spontaneous behaviour and the emesis and behavioural change induced by apomorphine (0.25 mg/kg, s.c.) were studied in the ferret. Domperidone was inactive to modify spontaneous behaviour but apomorphine-induced emesis and increased locomotor activity (distance travelled and velocity of movement; P<0.05); the emesis, but not the modification of locomotor activity was antagonized significantly (P<0.01) by domperidone. However, apomorphine did not modify significantly other behavioural measures (i.e. lip licking, rearing, burrowing, backward walking, curling-up activity, or defecatory frequency; P>0.05). The action of apomorphine to modify behaviour and its interaction with domperidone in this species is discussed in relation to animal models of nausea.
Descriptors: ferrets, antiemetics, apomorphine, behavior, domperidone pharmacology, vomiting, antiparkinson agents, motor activity, rats, chemically induced vomiting.

Lau, A.H.Y., K.K.W. Kan, H.W. Lai, M.P. Ngan, J.A. Rudd, and D.T.W. Yew (2003). Action of emetic drugs in the ferret and Suncus murinus (house musk shrew): New models of nausea? Journal of Veterinary Pharmacology and Therapeutics 26(Supplement 1): 157. ISSN: 0140-7783.
NAL Call Number: SF915.J63
Descriptors: emesis, ferret, musk shrew, animal models, emetic drugs, action, nausea, meeting abstract.
Notes: Proceedings of the 9th International Congress of the European Association for Veterinary Pharmacology and Toxicology, Lisbon, Portugal; July 13-18, 2003.

Lightbown, I.D., W.D. Miner, and J.D. Gale (2002). The anti-emetic activity of s(-)-eticlopride against morphine- and ipecacuanha-induced emesis in the conscious ferret. British Journal of Pharmacology 136(Proceedings Supplement): 61P. ISSN: 0007-1188.
Descriptors: ferret, anti emetic activity, s(-)-eticlopride, morphine, induced emesis, ipecacuanha, meeting abstract.
Notes: Proceedings of the British Journal of Pharmacology, Hatfield, Hertfordshire, UK; April 11-12, 2002.

Nakayama, H., H. Yamakuni, A. Nakayama, Y. Maeda, K. Imazumi, M. Matsuo, and S. Mutoh (2004). Diphenidol has no actual broad antiemetic activity in dogs and ferrets. Journal of Pharmacological Sciences 96(3): 301-306. ISSN: 1347-8613.
Abstract: Previous studies showed that diphenidol was effective on emetogens-induced pica, eating of non-nutritive substances, in rats, a model analogous to emesis in other species. We evaluated the actual antiemetic activity of diphenidol against four emetic stimuli in the dog and ferret, animals that possess an emetic reflex. In dogs, emetic responses to apomorphine were significantly prevented by diphenidol (3.2 mg/kg, i.v.), whereas diphenidol (3.2 mg/kg, i.v. x 2) showed a weak inhibition to the vomiting evoked by cisplatin. In ferrets, diphenidol (10 mg/kg, i.p.) exhibited a weak antiemetic activity on the emesis induced by copper sulfate and had no activity on emesis by loperamide. On the other hand, CP-122,721, a NK1-receptor antagonist, significantly reduced the emetic episodes to all four stimuli. These results suggest that the prediction of antiemetic activity of compounds in animals lacking an emetic reflex does not always correspond with actual antiemetic activity.
Descriptors: ferrets, dogs, antiemetics, piperidines pharmacology, vomiting, species specificity, chemically induced vomiting.

Nakayama, H., H. Yamakuni, M. Higaki, H. Ishikawa, K. Imazumi, M. Matsuo, and S. Mutoh (2005). Antiemetic activity of FK1052, a 5-HT3- and 5-HT4-receptor antagonist, in Suncus murinus and ferrets. Journal of Pharmacological Sciences 98(4): 396-403. ISSN: 1347-8613.
Descriptors: emesis, ferrets, Suncus murinus, antemetic activity, FK1052, receptor antagonists, cancer chemotherapy, cisplatin-induced emesis, copper sulfate.

Oland, L.D., J.S. Davison, and K.a. Sharkey (2003). Endocannabinoids inhibit emesis in the ferret. Digestive Disease Week Abstracts and Itinerary Planner 2003: Abstract No. W1430.
Descriptors: ferret, endocannabinoid, antiemetics, sedative effect, inhibition of vomiting, endogenous cannabinoid receptor agonists, anandamide, 2- arachidonylglycerol (2-AG), noladin.
Notes: Digestive Disease 2003, FL, Orlando, USA; May 17-22, 2003.

Osinski, M.A., M.E. Uchic, T. Seifert, T.K. Shaughnessy, L.N. Miller, M. Nakane, B.F. Cox, J.D. Brioni, and R.B. Moreland (2005). Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets. Pharmacology, Biochemistry, and Behavior 81(1): 211-219. ISSN: 0091-3057.
Abstract: Agents that activate the dopamine D2-like family of receptors elicit emesis in humans and other species with a vomiting/emetic reflex; however, the lack of dopamine receptor subtype selective agonists has hampered an understanding of which dopamine D2-like receptor subtype(s) contributes to the emetic response. In this study, stable cell lines expressing the ferret dopamine D2-long (D2L) and D4 receptors were used to characterize known dopamine agonists via radioligand binding and calcium ion flux assays, while emetic activity of these dopamine receptor agonists was determined in male ferrets. Latencies to first emetic event, average number of emetic episodes, and stereotypical behaviors which may be indicative of nausea were also determined. Agonists at dopamine D1-like and D4 receptors had no emetic effect in ferrets. Conversely, stimulation of dopamine D2 and/or D3 receptors resulted in a robust emetic response characterized by a relatively short latency (<15 min) and multiple emetic events. Competitive antagonists of dopamine D2-like receptors (domperidone, haloperidol) dose-dependently blocked the emetic response to PNU95666E, a dopamine D2 receptor selective agonist. Thus, dopamine D2 and/or D3 receptor agonists elicit emesis, while dopamine D1/D5 or D4 receptor-selective agonists are devoid of emetic properties.
Descriptors: ferrets, dopamine agonists, chemically induced vomiting, protein binding.

Rudd, J.A., M.P. Ngan, M.K. Wai, A.G. King, J. Witherington, P.L. Andrews, and G.J. Sanger (2006). Anti-emetic activity of ghrelin in ferrets exposed to the cytotoxic anti-cancer agent cisplatin. Neuroscience Letters 392(1-2): 79-83. ISSN: 0304-3940.
Abstract: Emesis may be modulated via multiple mechanisms. The actions of ghrelin suggest an ability to couple an induction of hunger with preparation of the stomach for ingestion of food. Such a process might reduce any tendency to vomit, so an anti-emetic activity of ghrelin was investigated in the ferret cisplatin-induced emesis model. In controls, intra-peritoneal cisplatin (10 mg/kg) induced 41.4+/-8.4 episodes of emesis comprising 310.4+/-55.3 retches and 28.8+/-6.9 vomits during the 6h observation; the latency to onset of the first emetic episode was 108.9+/-4.8 min. Intra-peritoneal ghrelin (1mg/kg, split as a 30 min pre- and 30 min-post dose) did not induce a change in behaviour or modify cisplatin-induced emesis (p>0.05). Intracerebroventricular (i.c.v.) administration (third ventricle) was achieved via a pre-implanted cannula. At the first emetic episode following cisplatin, ghrelin or vehicle (20 microl saline) was administered i.c.v. During the 30 min following the initial episode of emesis, control animals exhibited 18.0+/-2.6 emetic episodes comprising 160.3+/-24.1 retches and 13.8+/-2.7 vomits. Ghrelin 10 microg i.c.v. reduced the number of retches by 61.5% (p<0.05) and at a dose of 30 microg i.c.v. ghrelin reduced the number of episodes, individual retches and vomits by 74.4 (p<0.05), 80.4 (p<0.01), and 72.5% (p<0.05), respectively. At subsequent time periods there were no differences between ghrelin- or saline-treated animals (p>0.05). An ability of ghrelin to reduce emesis is consistent with a role in modulating gastro-intestinal functions and identifies a novel approach to the treatment of emesis.
Descriptors: ferrets, antiemetics, therapeutic use, antineoplastic agents, adverse effects, cisplatin, peptide hormones, therapeutic use, vomiting prevention, behavior, drug effects, disease models, dose response, drug interactions.

Sam, T.S., K.K. Kan, M.P. Ngan, J.A. Rudd, and J.H. Yeung (2003). Action of metyrapone and tetracosactrin to modify cisplatin-induced acute and delayed emesis in the ferret. European Journal of Pharmacology 466(1-2): 163-168. ISSN: 0014-2999.
Abstract: Cisplatin 5 mg/kg, i.p., induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of metyrapone and tetracosactrin and their potential interaction. The 11beta-hydroxylase enzymes inhibitor metyrapone 10-30 mg/kg, i.p., dose dependently potentiated the acute cisplatin-induce retching+vomiting response by up to 219% at the highest dose (P<0.001) but failed to affect significantly delayed emesis (P>0.05). The adrenocorticotropic hormone (ACTH) mimetic tetracosactrin 0.1 mg/kg, i.m., antagonised significantly the acute and delayed emetic response by 98% (P<0.01) and 75% (P<0.001), respectively. The anti-emetic action of tetracosactrin on acute but not delayed emesis was prevented by combination with metyrapone 10 mg/kg, i.p. Tetracosactrin 0.1 mg/kg, i.m., failed to modify apomorphine (0.25 mg/kg, s.c.)-induced emesis. The potential anti-emetic mechanism of action of metyrapone and tetracosactrin to modulate emesis is discussed.
Descriptors: ferrets, emesis, antiemetics, antineoplastic agents, cisplatin, cosyntropin, metyrapone, chemically induced vomiting, apomorphine administration, intramuscular injections, intraperitoneal injections, subcutaneous injections.

Sato, A., R. Saito, H. Ariumi, K. Honda, Y. Takano, and H.O. Kamiya (2002). Effects of cisplatin on monoamine levels in the area postrema and on emesis in ferrets. Japanese Journal of Pharmacology 88(Supplement 1): 195P. ISSN: 0021-5198.
Descriptors: ferrets, cisplatin, monoamine levels, postrema, emesis, meeting abstract.
Notes: 75th Annual Meeting of the Japanese Pharmacological Society, Kumamoto, Japan; March 13-15, 2002.

Shintani, T., R.L. Mori, and B.J. Yates (2003). Locations of neurons with respiratory-related activity in the ferret brainstem. Brain Research 974(1-2): 236-242. ISSN: 0006-8993.
Descriptors: ferret, brain stem, respiratory related activity, coughing, emesis, location, quiet breathing, motoneurons.

Simoneau, I.I., M. Hamza, H.P. Mata, F. Porrecca, and T.P.J. Malan (2002). Cannabinoids reduce morphine-induced emesis in ferrets. Anesthesiology Abstracts of Scientific Papers Annual Meeting(2000): Abstract No. 973.
Online: http://www.asa-abstracts.com
Descriptors: ferrets, emesis, morphine induced, cannabinoids, reduce, opioid analgesia, vomiting, meeting abstract.
Notes: 2000 Annual Meeting of the American Society of Anesthesiologists, San Francisco, CA, USA; October 16-18, 2000.

Tsuchiya, M., Y. Fujiwara, Y. Kanai, M. Mizutani, K. Shimada, O. Suga, S. Ueda, J.W. Watson, and A. Nagahisa (2002). Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret. Pharmacology 66(3): 144-152. ISSN: 0031-7012.
Abstract: The anti-emetic effects of a novel tachykinin NK(1) receptor antagonist, ezlopitant ((2S,3S-cis)-2-diphenylmethyl)- N-[(2-methoxy, 5-isopropylphenyl)methyl]-1-azabicyclo- [2.2.2]octan-3-amine), were investigated in ferrets. Ezlopitant inhibited [(3)H]substance P ([(3)H]SP) binding to the human, guinea pig, ferret and gerbil NK(1) receptors (K(i) = 0.2, 0.9. 0.6 and 0.5 nmol/l, respectively), but had no affinity to NK(2) and NK(3) receptors up to 1 micromol/l. Ezlopitant also inhibited SP-induced contraction of guinea pig trachea with a pA(2) value of 7.8, but had no effects on the baseline tension and maximum contractile response. In ferrets, ezlopitant, either orally (0.03-3 mg/kg) or subcutaneously (0.3-3 mg/kg), prevented acute retching and vomiting responses induced by intraperitoneal injection of cisplatin (10 mg/kg). In addition, repeated subcutaneous injection of ezlopitant significantly inhibited delayed retching and vomiting responses that occurred in ferrets treated with the lower dose of cisplatin (5 mg/kg, i.p.). Ezlopitant (0.1-1 mg/kg, s.c.) also produced a dose-dependent inhibition of hindpaw tapping induced by intracerebroventricular injection of [Sar(9),Met(O(2))(11)]SP in gerbils, which is known to be mediated by NK(1) receptors in the brain. These findings indicate that ezlopitant is a potent and selective NK(1) receptor antagonist, and that it inhibits both acute and delayed emetic reactions induced by cisplatin in ferrets via acting on NK(1) receptors in the central nervous system. Copyright 2002 S. Karger AG, Basel
Descriptors: ferrets, antiemetics, benzylamines, bicyclo compounds, heterocyclic therapeutic use, cisplatin toxicity, neurokinin 1 antagonists, chemically induced vomiting, cricetinae, Gerbillinae, guinea pigs, protein binding receptors.

Van Sickle, M.D., L.D. Oland, K. Mackie, J.S. Davison, and K.A. Sharkey (2003). Delta9-tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets. American Journal of Physiology. Gastrointestinal and Liver Physiology 285(3): G566-G576. ISSN: 0193-1857.
Abstract: The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Delta9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was approximately 0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.
Descriptors: ferrets, antiemetics, medulla oblongata, tetrahydrocannabinol, vagus nerve physiology, vomiting, area postrema, cisplatin, cannabinoid receptors, tissue distribution.

Yamakuni, H., H. Nakayama, S. Matsui, K. Imazumi, M. Matsuo, and S. Mutoh (2006). Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets. Journal of Pharmacological Sciences 101(1): 99-102. ISSN: 1347-8613.
Abstract: We evaluated the antiemetic effect of zacopride, a potent 5-HT3-receptor antagonist with 5-HT4-receptor agonist properties, on delayed emesis caused by cisplatin (5 mg/kg, i.p.) in ferrets, compared with granisetron, a selective 5-HT3-receptor antagonist. Multiple intravenous injections of zacopride at 1 mg/kg, a dose that completely inhibited acute emesis caused bycisplatin (10 mg/kg, i.v.), significantly reduced delayed emesis. Granisetron (3.2 mg/kg) also reduced delayed emesis but this failed to reach statistical significance. The present study suggests that a combined 5-HT3-receptor antagonist/5-HT4-receptor agonist, like zacopride, may be useful against both acute and delayed emesis induced by cancer chemotherapy.
Descriptors: antiemetics, antineoplastic agents, benzamides, serotonin antagonists, vomiting, ferrets, granisetron, time factors, chemically induced vomiting.

Yamakuni, H., H. Sawai Nakayama, K. Imazumi, Y. Maeda, M. Matsuo, T. Manda, and S. Mutoh (2002). Resiniferatoxin antagonizes cisplatin-induced emesis in dogs and ferrets. European Journal of Pharmacology 442(3): 273-278. ISSN: 0014-2999.
Abstract: We evaluated the antiemetic activity of resiniferatoxin, an ultrapotent capsaicin analogue, on cisplatin- and apomorphine-induced emesis in dogs, and on cisplatin-induced acute and delayed emesis in ferrets. In the dog, resiniferatoxin (10 microg/kg, s.c.) 30 min before the injection of cisplatin markedly prevented acute emesis induced by cisplatin. When animals were given resiniferatoxin (10 microg/kg, s.c.) 24 h prior to cisplatin, the emesis was still inhibited, but not significantly. Resiniferatoxin (10 microg/kg, s.c.) 30 min before the administration of apomorphine also significantly reduced the emetic responses induced by apomorphine in dogs. In the ferret, resiniferatoxin (10 microg/kg, s.c.) 30 min prior to cisplatin completely inhibited acute emesis caused by cisplatin (10 mg/kg, i.p.). When ferrets were given resiniferatoxin (10 microg/kg, s.c.) 16 h prior to cisplatin, the emesis was still significantly inhibited. Cisplatin (5 mg/kg, i.p.) induced both acute (0-24 h) and delayed (24-72 h) phase emesis, and a single injection of resiniferatoxin (10 microg/kg, s.c.) at 36 h after cisplatin significantly reduced subsequent emetic responses during the 36-72 h period. These results suggest that resiniferatoxin-related vanilloids may be useful drugs against both acute and delayed emesis induced by cancer chemotherapy.
Descriptors: ferrets, dogs, antineoplastic agents, cisplatin, diterpenes, vomiting, antineoplastic agents, antiparkinson agents, apomorphine, cisplatin toxicity.

Yanagihara, M., T. Mori, T. Ohonishi, H. Fukuda, N. Furukawa, and J. Col (2004). Investigation of neuronal circuit for induction of vomiting in the ferret. Anatomical Science International 79(August): 376. ISSN: 1447-6959.
Descriptors: ferret, vomiting, neuronal circuit, inducing vomiting.
Notes: 16th International Congress of the IFAA (International Federation of Associations of Anatomists) and the 109th Annual Meeting of the Japanese Association of Anatomists, Kyoto, Japan; August 22-27, 2004.

Yoshikawa, T. and N. Yoshida (2002). Effect of 6-hydroxydopamine treatment in the area postrema on morphine-induced emesis in ferrets. Japanese Journal of Pharmacology 89(4): 422-425. ISSN: 0021-5198.
Abstract: To investigate the role of catecholamine release in emesis, we examined the effects of pretreatment with 6-hydroxydopamine (6-OH-DA) administered into the area postrema in morphine-induced emesis in ferrets. In the 6-OH-DA pre-treated animals, the latency to the first emetic response induced by morphine hydrochloride (1.0 mg/kg, s.c.) was significantly prolonged and the number of retches and emetic episodes was markedly reduced. In the medulla oblongata, the levels of dopamine and homovanilic acid were reduced by 6-OH-DA pretreatment. These results suggest that catecholamine release in the medulla oblongata, mainly dopamine release, may play an important role in morphine-induced emesis in ferrets.
Descriptors: ferrets, postrema drug effects, morphine toxicity, oxidopamine, chemically induced vomiting, area postrema metabolism.

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