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Science1 publisher3 min readPublished

Vatinoxan prevented the eye bulging that common rat sedatives cause, Helsinki researchers report

The sedatives that push rats' eyes out of their sockets have been known since the 1980s and are still widely used. A University of Helsinki group says a drug developed for dogs prevents it, though the announcement does not include sample sizes.

The Scientist · Science desk

Illustration accompanying Vatinoxan prevented the eye bulging that common rat sedatives cause, Helsinki researchers report

What happened

  • Commonly used sedatives make rats' eyes bulge out of their sockets, an effect known since the 1980s, and the drugs that cause it remain widely used even though protruding eyes are exposed to painful injuries.
  • Minna Mustikka, a veterinary ophthalmology specialist at the University of Helsinki, tested vatinoxan in rats for her doctoral thesis and published the first paper in the Journal of Ocular Pharmacology and Therapeutics.
  • Emily Lindh reports that vatinoxan also blunted the sedative-driven rise in blood glucose and the excessive urine output in rats, in work published in Veterinary Anaesthesia and Analgesia and BMC Veterinary Research.
  • The vatinoxan product was developed by the same group with the Finnish company Vetcare for sedating dogs, and the group says it now appears to improve the safety of small rodents under anesthesia.

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Why it matters

  • decision A facility vet deciding whether to add a drug to a rodent protocol needs a magnitude and a control arm, and those numbers are in the three papers, so the decision has to wait on them.
  • constraint Honkavaara's species argument limits how far these results travel: validation in rats and mice holds for rats and mice, and rabbits, ferrets and primates each need their own study.
  • exposure The rodent claims come from the group that co-developed the canine vatinoxan product with Vetcare. Independent replication carries the weight before other laboratories change practice.
  • precedent The welfare evidence puts vatinoxan before ethics committees under the refine leg of the 3Rs, and the reduce claim in the group's rationale stays an inference.

Jussi Honkavaara has worked with vatinoxan for more than 20 years, and he heads the Helsinki group as associate professor of veterinary pharmacology [17]. He said the way a drug behaves in a new species is not worth trying to predict. "The same pharmaceutical agent can primarily boost circulation in dogs, alleviate constipation in horses and, in rodents, prevent the bulging of the eyes out of the sockets. Evolution has shaped the physiology of each species so uniquely that it is hardly worth trying to predict how new drugs could affect individual species. The answers will eventually be uncovered through high-quality basic research," Honkavaara said [18].

The eye work belonged to Minna Mustikka, a specialist in veterinary ophthalmology, whose doctoral thesis tested whether vatinoxan could help [5]. "Vatinoxan is proving to be the genuine article: We have demonstrated that in rats, it prevents the dramatic bulging of eyes associated with the use of common sedative combinations and alleviates other adverse effects occurring inside the eye. The findings have already been groundbreaking for the welfare of laboratory rats," Mustikka said [7].

Emily Lindh took the circulation side, in rats and mice [9]. "Sedation and anesthesia are necessary for the humane treatment of animals, but the adverse effects of the drugs used should not compromise the reliability of research findings. In my doctoral thesis, I demonstrate that vatinoxan improves tissue oxygenation in rats by reducing the adverse circulatory effects of sedatives," Lindh said [10].

The announcement identifies the drugs only as commonly used sedatives and common sedative combinations, and it leaves the sample sizes and effect sizes to the three journals it names [20][21][8][12]. The group's framing is that substandard anesthesia can cause suffering, distort experimental results and force researchers to repeat tests on more animals [1]. Blood glucose and urine output are quantities rat studies measure, and Lindh reports that vatinoxan held down the sedative-driven rise in both [11]. The support here for the repeat-experiment argument is those physiological findings.

Anna Meller and Karoliina Alm, veterinarians at the Laboratory Animal Centre, have been in the studies from the beginning [15], and they put weight on what happens before an experiment starts. "These studies have confirmed the notion that rats and mice soon get used to handling by humans when it is competent and on the animal's terms. This area should be further developed in laboratory veterinary medicine, as it would improve the reliability of research findings alongside animal welfare," Alm said [16]. Marja Raekallio, a senior university lecturer who has been involved in the vatinoxan research since the start, considers the rodent findings particularly unambiguous [19].

The 3R principles guide laboratory animal research worldwide: reduce the number of animals used, replace animal testing with other methods where possible, refine methods to minimize harm [14]. "The main goal of my doctoral research is to improve research methods in accordance with the 3R principles. Rats are still one of the most widely used species in biomedical research," Lindh said [13].

What to watch

  • Replication of the exophthalmos result by a group with no involvement in the Vetcare product.
  • Whether the underlying papers name the specific sedative combinations and report effect sizes and control arms.
  • Guidance from a national laboratory animal welfare body on pairing vatinoxan with rodent sedation protocols.
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