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Equine veterinary journal2025; doi: 10.1111/evj.14499

Effects of vatinoxan on gastrointestinal motility, sedation, and antinociception during and after long-lasting detomidine infusion in horses.

Abstract: Sedation in horses is typically achieved using alpha-2 adrenoceptor agonists, although their use is associated with multiple side effects. A peripheral alpha-2 adrenoceptor antagonist, vatinoxan, can alleviate many of these. Objective: To evaluate the effects of vatinoxan infusion on gastrointestinal motility, sedation, and antinociception in horses sedated with detomidine infusion. Methods: Randomised, blinded cross-over in vivo experiments. Methods: Eight horses were given two 4-h infusions: detomidine (0.01 mg/kg + 0.015 mg/kg/h IV) (DET) and a combination of detomidine and vatinoxan (0.15 mg/kg + 0.05 mg/kg/h IV) (DET + VAT). Plastic marker balls were administered via nasogastric entubation before the start of the infusion. Borborygmi score was monitored. The expelling of balls and faecal output were repeatedly monitored for 72 h after the infusion. Sedation score (SS) and antinociception were monitored during the infusion. Results: Borborygmi score remained significantly higher during DET + VAT infusion and the following hour than with DET (p < 0.05) at different time points. Median (range) cumulative weight of faeces was significantly higher with DET + VAT [6.25 kg (3.52-8.65)] than with DET [2.85 kg (1.7-6.6)] (p = 0.007) during the first 8 h after the end of infusion. The markers were expelled significantly faster after DET (mean AUC 3928 ± 1620) than after DET + VAT (mean AUC 2460 ± 1199) infusion (p = 0.02). All animals were appropriately sedated. Median SS was significantly lower at 60 min during DET + VAT [7 (5-7)] than during DET [7.5 (7, 8)] (p = 0.04). No other significant differences were detected in SS or antinociception between treatments. Conclusions: Vatinoxan significantly improved the borborygmi score. Horses treated with DET + VAT passed more faeces in the initial period after infusion, although the expelling of plastic balls was faster with DET. Combining vatinoxan with detomidine infusion may slightly reduce the level of sedation in the initial phase of infusion. Vatinoxan may improve gastrointestinal motility in horses treated with detomidine infusion. Unassigned: Agonistas dos receptores adrenérgicos alfa‐2 são comumente utilizados para sedação em cavalos, embora seu uso esteja associado a múltiplos efeitos colaterais. Um antagonista periférico do receptor adrenérgico alfa‐2, vatinoxan, pode aliviar muitos desses efeitos. Objective: Avaliar os efeitos da infusão de vatinoxan na motilidade gastrointestinal, sedação e antinocicepção em cavalos sedados com infusão de detomidina. Unassigned: Estudo in vivo, randomizado, cego e cruzado. MÉTODOS: Oito cavalos receberam duas infusões de quatro horas: detomidina (0,01 mg/kg + 0,015 mg/kg/h IV) (DET) e uma combinação de detomidina e vatinoxan (0,15 mg/kg + 0,05 mg/kg/h IV) (DET + VAT). Bolas marcadoras de plástico foram administrada via tubo nasogástrico antes do início da infusão. O escore de borborigmos foi monitorado. A expulsão das bolas e a produção faecal foram monitoradas repetidamente por 72 horas após a infusão. O escore de sedação (ES) e a antinocicepção foram monitorados durante a infusão. Results: O escore de borborigmos permaneceu significativamente mais alto durante a infusão de DET + VAT e na hora seguinte do que com DET (p < 0,05) em diferentes momentos. O peso cumulativo mediano (intervalo) das fezes foi significativamente maior com DET + VAT [6,25 kg (3,52‐8,65)] do que com DET [2,85 kg (1, 6)] (p = 0,007) nas primeiras 8 horas após o fim da infusão. Os marcadores foram expelidos significativamente mais rápido após DET (média AUC 3928 ± 1620) do que após a infusão de DET + VAT (média AUC 2460 ± 1199; p = 0,02). Todos os animais foram adequadamente sedados. O ES mediano foi significativamente menor aos 60 minutos durante DET + VAT [7 (5–7)] do que durante DET [7,5 (7, 8)] (p = 0,041). Nenhuma outra diferença foi detectada no ES ou na antinocicepção entre os tratamentos. CONCLUSÕES: Vatinoxan melhorou significativamente o escore de borborigmos. Cavalos tratados com DET + VAT passaram mais fezes no período inicial após a infusão, embora a expulsão de bolas de plástico tenha sido mais rápida com DET. A combinação de vatinoxan com a infusão de detomidina pode reduzir ligeiramente o nível de sedação na fase inicial da infusão. Vatinoxan talvez melore a motilidade gastrointestinal em cavalos tratados com infusão de detomidina.
Publication Date: 2025-03-20 PubMed ID: 40110892DOI: 10.1111/evj.14499Google Scholar: Lookup
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  • Journal Article

Summary

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The research investigates the effect of the drug vatinoxan, which is an antagonist, when used in combination with detomidine, a sedative frequently used in horses. The study shows that vatinoxan can help to alleviate the side effects of detomidine, primarily the decrease in gastrointestinal motility.

Objective

  • The main aim of this research was to study the impacts of vatinoxan infusion on three key areas: gastrointestinal motility, sedation, and antinociception (relief from pain) in horses when used with detomidine.

Method

  • The researchers conducted an in vivo experiment involving eight horses. The horses were randomly assigned to one of two treatment groups: one group received detomidine only (DET) and the other received a combination of detomidine and vatinoxan (DET + VAT).
  • Each horse participated in two four-hour infusion sessions where they were administered the respective treatments. For the DET group, they received 0.01mg/kg initially followed by a dose of 0.015mg/kg/hour of detomidine, while the DET + VAT group received an initial dose of 0.15mg/kg of vatinoxan followed by 0.05mg/kg/hour in addition to the detomidine.
  • Prior to the infusions, each horse was given plastic marker balls using a nasogastric tube. Observations were then made for gastrointestinal activity (borborygmi score), sedation levels and the passage of feces and marker balls for up to 72 hours post-infusion.

Findings

  • The results showed that the DET + VAT group had significantly higher borborygmi scores during the infusion and up to an hour afterwards compared to the DET group. This suggests that the combination of detomidine and vatinoxan improves gastrointestinal motility.
  • Overall, horses in the DET + VAT group passed more feces in the initial eight hours after the infusion ended. However, the transit time of the plastic markers was faster in the DET group, indicating faster gastrointestinal transit in the absence of vatinoxan.
  • While all animals were appropriately sedated, at the 60-minute mark, the DET + VAT group showed a slightly reduced sedation score compared to the DET group.
  • No significant differences between the two groups were observed in terms of pain relief (antinociception) during the study.

Conclusion

  • The findings of the study conclude that vatinoxan can significantly improve gastrointestinal motility in horses sedated with detomidine. It also suggested a slight reduction in the level of sedation in the initial phase of sedation when both drugs were used in combination.

Cite This Article

APA
Obrochta B, Tapio H, Raekallio M, Gracia Calvo LA, Pöyhönen RR, Hagman K, Jantunen N, Karikoski N. (2025). Effects of vatinoxan on gastrointestinal motility, sedation, and antinociception during and after long-lasting detomidine infusion in horses. Equine Vet J. https://doi.org/10.1111/evj.14499

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Obrochta, Bartlomiej
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Tapio, Heidi
  • Veterinary Teaching Hospital, University of Helsinki, Helsinki, Finland.
Raekallio, Marja
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Gracia Calvo, Luis Alfonso
  • Veterinary Teaching Hospital, University of Helsinki, Helsinki, Finland.
Pöyhönen, Rebecca Rivera
  • Faculty of Veterinary Medicine, Estonian University of Life Sciences, Tartu, Estonia.
Hagman, Kati
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
Jantunen, Noora
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Karikoski, Ninja
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.

Grant Funding

  • Vetcare

References

This article includes 32 references
  1. Laurenza C, Ansart L, Portier K. Risk factors of anesthesia‐related mortality and morbidity in one equine hospital: a retrospective study on 1,161 cases undergoing elective or emergency surgeries.. Front Vet Sci 2020;6:514.
  2. Gozalo‐Marcilla M, Bettschart‐Wolfensberger R, Johnston M, Taylor PM, Redondo JI. Data collection for the fourth multicentre confidential enquiry into perioperative equine fatalities (CEPEF4) study: new technology and preliminary results.. Animals 2021;11(9):2549.
    doi: 10.3390/ani11092549google scholar: lookup
  3. Bonomelli N. Bonilla AG (2022) standing surgery among equine board certified surgeons: survey regarding current use and trends.. Equine Vet J 2023;55(6):1045–1057.
    doi: 10.1111/evj.13920google scholar: lookup
  4. Bettschart‐Wolfensberger R, Clarke KW, Vainio O, Aliabadi F, Demuth D. Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.. Res Vet Sci 1999;67:41–46.
  5. Wilson D, Bohart G, Evans A, Robertson S, Rondenay Y. Retrospective analysis of detomidine infusion for standing chemical restraint in 51 horses.. Vet Anaesth Analg 2002;29:54–57.
  6. Merritt AM, Burrow JA, Hartless CS. Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on equine duodenal motility.. Am J Vet Res 1998;59:619–623.
  7. Koenig JB, Martin CEW, Nykamp SG, Mintchev MP. Use of multichannel electrointestinography for noninvasive assessment of myoelectrical activity in the cecum and large colon of horses.. Am J Vet Res 2008;69:709–715.
  8. Elfenbein JR, Sanchez LC, Robertson SA, Cole CA, Sams R. Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses.. Vet Anaesth Analg 2009;36:162–172.
  9. Mama KR, Grimsrud K, Snell T, Stanley S. Plasma concentrations, behavioural and physiological effects following intravenous and intramuscular detomidine in horses.. Equine Vet J 2009;41:772–777.
    doi: 10.2746/042516409x421624google scholar: lookup
  10. Rezende ML, Grimsrud KN, Stanley SD, Steffey EP, Mama KR. Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse.. J Vet Pharmacol Ther 2015;38:15–23.
  11. Knaus A, Muthig V, Schickinger S, Moura E, Beetz N, Gilsbach R. α2‐Adrenoceptor subtypes—unexpected functions for receptors and ligands derived from gene‐targeted mouse models.. Neurochem Int 2007;51:277–281.
  12. DiMaio Knych HK, Covarrubias V, Steffey EP. Effect of yohimbine on detomidine induced changes in behavior, cardiac and blood parameters in the horse.. Vet Anaesth Analg 2012;39:574–583.
  13. Box JR, Karikoski NP, Tanskanen HE, Raekallio MR. The effects of an alpha‐2‐adrenoceptor agonist, antagonist, and their combination on the blood insulin, glucose, and glucagon concentrations in insulin sensitive and dysregulated horses.. Vet J 2021;269:105610.
  14. Zullian C, Menozzi A, Pozzoli C, Poli E, Bertini S. Effects of α2‐adrenergic drugs on small intestinal motility in the horse: an in vitro study.. Vet J 2011;187:342–346.
  15. Clineschmidt BV, Pettibone DJ, Lotti VJ, Hucker HB, Sweeney BM, Reiss DR. A peripherally acting alpha‐2 adrenoceptor antagonist: L‐659,066.. J Pharmacol Exp Ther 1988;245:32–40.
  16. Honkavaara JM, Raekallio MR, Syrja PM, Pypendop BH, Knych HK, Kallio‐Kujala IJ. Concentrations of medetomidine enantiomers and vatinoxan, an α2‐adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs.. Vet Anaesth Analg 2020;47:47–52.
  17. Vainionpää MH, Raekallio MR, Pakkanen SA, Ranta‐Panula V, Rinne VM, Scheinin M. Plasma drug concentrations and clinical effects of a peripheral alpha‐2‐adrenoceptor antagonist, MK‐467, in horses sedated with detomidine.. Vet Anaesth Analg 2013;40:257–264.
  18. Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC. Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant‐rate medetomidine infusion in standing horses.. Equine Vet J 2019;51:646–652.
  19. Tapio HA, Raekallio MR, Mykkänen A, Mama K, Mendez‐Angulo JL, Hautajärvi H. Effects of MK‐467 hydrochloride and hyoscine butylbromide on cardiorespiratory and gastrointestinal changes induced by detomidine hydrochloride in horses.. Am J Vet Res 2018;79:376–387.
  20. De Vries A, Pakkanen SA, Raekallio MR, Ekiri A, Scheinin M, Taylor PM. Clinical effects and pharmacokinetic variables of romifidine and the peripheral α2‐adrenoceptor antagonist MK‐467 in horses.. Vet Anaesth Analg 2016;43:599–610.
  21. Rohrbach H, Korpivaara T, Schatzmann U, Spadavecchia C. Comparison of the effects of the alpha‐2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses.. Vet Anaesth Analg 2009;36:384–395.
  22. Ross MW, Donawick WJ, Sellers AF, Lowe JE. Normal motility of the cecum and right ventral colon in ponies.. Am J Vet Res 1986;47:1756–1762.
  23. Lester GD, Merritt AM, Neuwirth L, Vetro‐Widenhouse T, Steible C, Rice B. Myoelectric activity of the ileum, cecum, and right ventral colon, and cecal emptying of radiolabeled markers in clinically normal ponies.. Am J Vet Res 1998;59:313–319.
  24. Sasaki N, Yoshihara T. The effect of motilin on the regulation mechanism of intestinal motility in conscious horses.. J Vet Med Sci 1999;61:167–170.
  25. Burns GA, Cummings JF. Equine myenteric plexus with special reference to the pelvic flexure pacemaker.. Anat Rec 1991;230:417–424.
  26. Gough RL, McGovern KF, Bladon BM, Carmichael LA. Caecal dysfunction following standing surgical procedures.. Vet Med Sci 2022;8(5):1930–1935.
    doi: 10.1002/vms3.882google scholar: lookup
  27. Bennett RC, Salla KM, Raekallio MR, Hänninen L, Rinne VM, Scheinin M. Effects of MK‐467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs.. J Vet Pharmacol Ther 2016;39:336–343.
  28. Bennett RC, Salla KM, Raekallio MR, Scheinin M, Vainio OM. Effects of the α2‐adrenoceptor agonist medetomidine on the distribution and clearance of alfaxalone during coadministration by constant rate infusion in dogs.. Am J Vet Res 2017;78(8):956–964.
    doi: 10.2460/ajvr.78.8.956google scholar: lookup
  29. Huuskonen V, Restitutti F, Honkavaara JM, Raekallio MR, Männikkö S, Scheinin M. Investigation of the effects of vatinoxan on somatic and visceral antinociceptive efficacy of medetomidine in dogs.. Am J Vet Res 2020;81:299–308.
  30. Elfenbein JR, Robertson SA, Corser AA, Urion RJ, Sanchez LC. Systemic effects of a prolonged continuous infusion of ketamine in healthy horses.. J Vet Intern Med 2011;25:1134–1137.
  31. Patton ME, Leise BS, Baker RE, Andrews FM. The effects of bit chewing on borborygmi, duodenal motility, and gastrointestinal transit time in clinically normal horses.. Vet Surg 2022;51(1):88–96.
    doi: 10.1111/vsu.13745google scholar: lookup
  32. Patton ME, Andrews F, Wong D, Bogers SH, McKenzie HC III, Byron CR. The effects of bit chewing on gastric emptying and orocecal transit times in clinically normal horses.. Equine Vet Educ 2024;36:78–79.
    doi: 10.1111/eve.110_14008google scholar: lookup

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