AIM: This paper is aimed to deliver an up to date on the novel active ingredients that are expected to be launched on the veterinary market in the next year, discussing their pharmacokinetic, pharmacodynamic and safety profiles. Pets are treated as members of the family and pet owners demand the same level of care they expect for themselves. This change in attitude has led to rapid evolution in the field of pharmacology with trend towards the development of more effective and innovative veterinary therapies with higher potency, more rapid speed of action and fewer side effects. Two new active ingredients are under pivotal trials to get into the drug veterinary market: grapriprant (GP) and soluble epoxide hydrolase inhibitors (sEH). Prostaglandin E2 (PGE2) is a key mediator of inflammation and pain, exerts its effects via four receptors, EP1, EP2, EP3 and EP4. The EP4 receptor is the primary mediator of the PGE2-elicited sensitization of sensory neurons and PGE2-elicited inflammation. The EP4 receptor is not the only receptor involved in inflammation and pain, but its inhibition may mediate central sensitization and play a role in chronic pain in humans and animals. GP is a novel analgesic and anti-inflammatory drug in the piprant class that works as a selective EP4 prostaglandin receptor antagonist (PRA) (1). All arachidonic acid metabolites, which encompass the prostanoids, leukotrienes and epoxy fatty acids, are bioactive lipids that play a positive or negative role in inflammation and pain, specifically under pathological conditions. The allogeneic and pro-inflammatory prostanoids and leukotrienes drive and maintain inflammation, while the anti-inflammatory and analgesic epoxy fatty acids epoxyeicosatrienoic acids (EETs) reduce and resolve inflammation. EETs are generated by cytochrome P450 enzymes and have various beneficial biological effects, not only do they have anti-inflammatory and analgesic actions but they also have protective effects on the cardiovascular system and kidney as recently reported in the literature. Unfortunately EETs are very instable and are rapidly converted into the corresponding 1, 2 diols (dihydroxyeicosatrienoates, DHETs), characterized by a pro-inflammatory actions. Inhibiting the enzyme that carries out this reaction, the soluble epoxide hydrolase (sEH), the EET levels can be stabilized with expected beneficial biological effects (2). During the presentation the recent studies performed on these two class of drug will be discussed. 1 Giorgi 2015 Am J Anim Vet Sci 10, 53-56 2 Lee et al. 2014 Israeli J Vet Med 69, 55-61

NOVEL ACTIVE COMPOUNDS FOR NEW THERAPIES FOR PAIN AND INFLAMMATION IN VETERINARY MEDICINE: AN UPDATE

GIORGI, MARIO
2016-01-01

Abstract

AIM: This paper is aimed to deliver an up to date on the novel active ingredients that are expected to be launched on the veterinary market in the next year, discussing their pharmacokinetic, pharmacodynamic and safety profiles. Pets are treated as members of the family and pet owners demand the same level of care they expect for themselves. This change in attitude has led to rapid evolution in the field of pharmacology with trend towards the development of more effective and innovative veterinary therapies with higher potency, more rapid speed of action and fewer side effects. Two new active ingredients are under pivotal trials to get into the drug veterinary market: grapriprant (GP) and soluble epoxide hydrolase inhibitors (sEH). Prostaglandin E2 (PGE2) is a key mediator of inflammation and pain, exerts its effects via four receptors, EP1, EP2, EP3 and EP4. The EP4 receptor is the primary mediator of the PGE2-elicited sensitization of sensory neurons and PGE2-elicited inflammation. The EP4 receptor is not the only receptor involved in inflammation and pain, but its inhibition may mediate central sensitization and play a role in chronic pain in humans and animals. GP is a novel analgesic and anti-inflammatory drug in the piprant class that works as a selective EP4 prostaglandin receptor antagonist (PRA) (1). All arachidonic acid metabolites, which encompass the prostanoids, leukotrienes and epoxy fatty acids, are bioactive lipids that play a positive or negative role in inflammation and pain, specifically under pathological conditions. The allogeneic and pro-inflammatory prostanoids and leukotrienes drive and maintain inflammation, while the anti-inflammatory and analgesic epoxy fatty acids epoxyeicosatrienoic acids (EETs) reduce and resolve inflammation. EETs are generated by cytochrome P450 enzymes and have various beneficial biological effects, not only do they have anti-inflammatory and analgesic actions but they also have protective effects on the cardiovascular system and kidney as recently reported in the literature. Unfortunately EETs are very instable and are rapidly converted into the corresponding 1, 2 diols (dihydroxyeicosatrienoates, DHETs), characterized by a pro-inflammatory actions. Inhibiting the enzyme that carries out this reaction, the soluble epoxide hydrolase (sEH), the EET levels can be stabilized with expected beneficial biological effects (2). During the presentation the recent studies performed on these two class of drug will be discussed. 1 Giorgi 2015 Am J Anim Vet Sci 10, 53-56 2 Lee et al. 2014 Israeli J Vet Med 69, 55-61
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/813779
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