Cerenia

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Maropitant.jpg

Maropitant (Cerenia™) is a NK-1 neurokinin receptor antagonist for use as an antiemetic agents for control of vomiting in dogs[1].

Several anti-emetic or tranquilising agents are commonly prescribed off-label for the treatment of motion sickness in pets. These include agents such as acepromazine, chlorpromazine, ondansetron and metoclopramide. Non-prescription drugs such as diphenhydramine, meclizine and dimenhydrinate are also used. The effectiveness of these medications in the treatment of motion sickness is often poor and all come with a variety of side effects which include sedation, ataxia and hypotension. Maropitant administered 1, 2 or 10 hrs before transportation reduced the incidence of motion induced emesis by approximately 80% compared with placebo treatment.

Maropitant is well tolerated in the dog as demonstrated in acute toleration studies and during a 15 day safety study. Subcutaneous administrations of maropitant at up to 5.0 mg/kg produced no abnormalities in behaviour, appetite or level of consciousness. Physical examination revealed no evidence of neurological or cardiovascular abnormalities. Repeated administration of maropitant at a daily dose of 0.5 mg/kg for four consecutive days did not reveal any adverse clinical signs.

Although substance P was identified in the 1930s from extracts of brain and intestine, it wasn't until the early 1990s that its role in emesis became appreciated. Substance P is a member of the tachykinin family of peptides, all of which share the common C-terminal amino acid sequence Phe-X-Gly-Leu-Met.NH2. Mammalian tachykinins also include neurokinin A and neurokinin B[2]. Tachykinin receptors include tachykinin NK-1 receptor, tachykinin NK-2 receptor and tachykinin NK-3 receptor. Substance P is the most potent tachykinin at the NK-1 receptor whereas neurokinin A exhibits highest affinity for the tachykinin NK-2 receptor and neurokinin B has the greatest affinity at the tachykinin NK-3 receptor[3].

Multiple lines of evidence indicate that substance P plays an important role in eliciting emesis. Substance P is found in high concentrations in areas of the brain stem involved in emesis including the nucleus solitarius, the area postrema and the dorsal motor nucleus of the vagus. Microinjection of substance P into the brain stem elicits an immediate emetic response[4].

Resiniferatoxin, a naturally occurring analgesic compound that depletes substance P, was found to have broad spectrum anti-emetic effects in the ferret[5]. These data suggested that an NK-1 receptor antagonist might have anti-emetic properties. It is now well recognised that NK-1 receptor antagonists, including Maropitant, can be used to inhibit emesis produced by a wide variety of emetic stimuli, in contrast to the more limited efficacy observed with other commercially available anti-emetics such as 5-HT3 receptor antagonists[6].

Recommended dosages in dogs is 1 - 8 mg/kg IV, SQ or orally once daily[7].

References

  1. De La Puente-Redondo, VA et al (2007) The anti-emetic efficacy of maropitant (Cerenia™), in the treatment of ongoing emesis caused by a variety of underlying clinical aetiologies in canine patients in Europe. The Journal of Small Animal Practice. 48: 93-98
  2. McLean, S (1996) Nonpeptide antagonists of the NK-1 tachykinin receptor. Medicinal Research Reviews 16: 297-317
  3. Ariumi, H et al (2000) The role of tachykinin NK-1 receptors in the area postrema of ferrets in emesis. Neuroscience Letters 286: 123-126
  4. Hargreaves, R. (2002) Imaging substance P receptors (NK-1) in the living human brain using positron emission tomography. The Journal of Clinical Psychiatry. 63(11):18-24
  5. Rupniak, NM & Kramer MS (1999) Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK-1) antagonist. Trends in Pharmacological Sciences 20: 485-490
  6. Saria, A (1999) The tachykinin NK-1 receptor in the brain: pharmacology and putative functions. European Journal of Pharmacology 375: 51-60
  7. Lesman SP et al (2012) The pharmacokinetics of maropitant citrate dosed orally to dogs at 2 mg/kg and 8 mg/kg once daily for 14 days consecutive days. J Vet Pharmacol Ther Nov 20