Maropitant (a.k.a Cerenia)
Cerenia, generically known as Maropitant, is a neurokinin-1 receptor antagonist. It mediates effects of central and peripheral substance P, an excitatory neurotransmitter and is in a class of peptides known as neurokinins. Substance P binds neurokinin-1 receptors which are G protein coupled receptors. As an antagonist, maropitant and others like it, blocks the action of substance P.
Where are neurokin-1 receptors located?
They are located in the central nervous system, heart and blood vessels, genitourinary system, immune system , and gastrointestinal tract.
What are the effects of Cerenia in the body?
These neurokin-1 receptors are involved in blood cell production, wound healing, neurogenic inflammation, cell survival, cell proliferation, pain transmission, endocrine and paracrine secretions, dilation of blood vessels. They are involved with neuronal transmission associated with depression, stress. Cerenia antagonizes the affects in these areas as well as acts on two areas in the central nervous system to stop vomiting: area postrema and nucleus tractus solitaries.
So if rabbits and rodents cannot vomit, why is it often used in exotic companion mammals?
While the anti-vomiting effects in rabbits and rodents not seem as important since they cannot vomit, it does not necessarily mean they cannot feel nausea. Efficacy of maropitant for preventing vomiting is also associated with pmotion sickness in dogs where it blocks final common pathway in the vomiting center of the brain. Studies showed it was very effective in preventing vomiting in dogs premedicated with hydromorphone, an opioid drug often associated with nausea and vomiting in patients. There are reports on Veterinary Information Network as well about its use with rabbits during head tilt and it is thought to maybe be helpful to reduce nausea from vestibular disease. It is also used in ferrets and birds as an anti-regurgitation drug.
What about its use in pain control?
As a neurokinin-1 receptor antagonist, Maropitant has shown to reduce anesthetic requirements of dogs undergoing surgery and can be used to reduce visceral pain. In rabbits, Maropitant reduced the viscerosensory response caused by colorectal distention and it is often in rabbits and guinea pigs as pain control for gastrointestinal stasis.
It also has anti-itch effects!
Since neurokinin-1 receptors are involved in mediating some itch pathways. Substance P is found in nerve fibers in the skin and it plays a significant role in the nerve pathways that are involved in inchiness. antagonizing, or blocking these pathways, can be helpful to reduce itch. Studies have shown similar drugs reducing itch in humans and Maropitant signficantly reduced the itchiness of ulcerative dermtitis lesions in mice.
It can also reduce the creation of abdominal adhesions forming after surgery!
Antagonizing neurokinin 1 receptors decreases postoperative adhesion formation and increases peritoneal fibrinolytic activity. Research in a rat model with the use of a neurokinin-1 receptor antagonist (NK-1RA) was found to decrease postoperative peritoneal adhesion formation by up to 53% at higher doses studied compared to saline controls. This research indicated that the antagonist used blocked the binding of substance P to neurokinin receptors. Left unblocked, substance P is proinflammatory and results proliferation of scar tissue and stimulates excessive blood vessel formation. Furthermore, antagonism appears to increase expression of tissue-type plasminogen activator an important enzyme in the production of plasmin, a protein that breaks down fibrin and scar tissue production. Research in rabbits has shown that intestinal adhesions can be reduced compared to controls when tissue-type plasminogen activator is given intraperitoneally.
But wait… there’s more… how about in respiratory disease
Maropitant has been used to treat canine chronic bronchitis. Substance P acts on the neurokinin-1 receptor in airway inflammation and the cough reflex. Antagonizing substance P showed a significant decrease in cough frequency and severity but no change in inflammation.
So are their side effects for Maropitant we should consider?
Some recommend not giving for more than 5 days in a row since the enzyme responsible for its metabolism, CYP2D15, becomes saturated. It should also be used with caution with highly protein bound drugs as these drugs compete with Maropitant for protein binding and there can be increases in unbound Maropitant in the blood. Also it should be used with caution with calcium channel antagonists as maropitant has an affinity for Ca and K channels. Excessive use may also decrease intestinal motility and it induced intestinal motility disorder in mice.
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