(S)-Medetomidine

(S)-Medetomidine, aka dexmedetomidine, is a veterinary drug that is supplied as a racemic mixture¹ with its nonactive (R)-enantiomer². The racemate first appeared in the literature in 1961, when L. M. Bezeau*, C. B. Bailey, and S. B. Slen at the Canada Agriculture Research Station (Lethbridge, AB) used it in a study of silica urolithiasis (a kidney disease) in beef cattle.

The first appearance of the (S)-enantiomer was in 1988, when Ira S. Segal and co-workers at Hennepin County Medical Center (Minneapolis) reported on the effects of both medetomidine enantiomers on the anesthetic requirements of laboratory rats anesthetized with halothane³. Their principal finding was that using (S)-medetomidine decreased the dose requirement for halothane to achieve full anesthesia; the (S)-enantiomer had no effect. The same year, the Hennepin County researchers obtained similar results in a study of dog anesthesia.

(S)-Medetomidine is an α₂-adrenergic agonist, meaning that it causes a response from α₂-adrenergic receptors and has effects similar to those of adrenaline⁴, last week’s Molecule of the Week. As the hydrochloride⁵ of its racemate, medetomidine has been commercialized as a sedative and analgesic for dogs. The US Food and Drug Administration approved its use for that purpose in 1996. In 2022, FDA approved the combination of rac-medetomidine hydrochloride and vatinoxan hydrochloride⁶, an α₂-adrenergic antagonist that counteracts vasoconstriction and hypertension caused by medetomidine.

Medetomidine has another, entirely different, use: as an ingredient in marine paints to prevent biofouling by barnacle (Crustacea subclass Cirripedia) larvae and other crustacean larvae. In 2012, Eric R. Holm at the Naval Surface Warfare Center (West Bethesda, MD) described medetomidine as a long-sought commercial solution for preventing biofouling of ships’ hulls.

More recent findings have shown, however, that medetomidine can adversely affect fish and other marine and aquatic animals. In a study published the year before Holm’s article, Anna Lennquist and co-workers at the University of Gothenburg (Sweden) reported that exposure to the compound interfered with carbohydrate metabolism in rainbow trout (Oncorhynchus mykiss).

Finally, medetomidine has shown up as an adulterant in illicit drugs. This past July, Phil Durney and numerous collaborators at Thomas Jefferson University and Friends Research Institute (both in Philadelphia) described a study of the effects of the metabolite 3-hydroxymedetomidine⁷ in urine samples taken from intoxicated subjects and those suffering from withdrawal symptoms. The former group exhibited sedation, bradycardia, and often hypotension, whereas the latter presented with life-threatening tachycardia, hypertension, and often encephalopathy.

1. CAS Reg. No. 86347-14-0.
2. CAS Reg. No. 119717-21-4.
3. CAS Reg. No. 151-67-7.
4. CAS Reg. No. 51-43-4.
5. CAS Reg. No. 86347-15-1.
6. CAS Reg. No. 130466-38-5.
7. No CAS Reg. No. assigned.