WHAT’S NEW IN MOLECULES WITH POTENTIAL FOR USE IN VETERINARY MEDICINE?

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 (Giorgi, 2012). Treatment of pain and inflammation are important considerations in human medicine. Likewise, in veterinary medicine in recent years, pain has been shown to dramatically affect animal welfare and production and interest in its treatment is increasing (Kim and Giorgi, 2013). Furthermore, veterinary pharmacology still has a reduced drug armamentarium and human drugs are increasingly being investigated for veterinary use. It has only been in recent years that analgesics have been marketed exclusively for veterinary patients. Therefore, it is pivotal that new human drugs and therapies be tested also in veterinary species (Giorgi, 2012). The two main classes of drug used to reduce pain in animals are opioids and Nonsteriodal Anti-Inflammatory Drugs (NSAIDs). Recently, some of the novel molecules in these classes marketed for the human field have been successfully tested on veterinary species (Lavy et al., 2011; Giorgi and Yun, 2012; Giorgi et al., 2012; 2013; Lee et al., 2013; De Vito et al., 2014). In the last few years, many researchers have directed attention towardsarachidonic acid (AA) metabolism and in particular, to the cytochrome P450 (CYP450) enzymes. These have been referred to as the third pathway of AA metabolism, in addition to Cyclooxygenases (COX) and Lipoxygenases (LOX) (Fleming, 2011). All AA metabolites, which encompass theprostanoids, 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 prostanoidsand leukotrienes drive and maintain inflammation, while the anti-inflammatory and analgesic epoxy fatty acids epoxyeicosatrienoic acids (EETs) reduce and resolve inflammation (Wagner et al., 2011). Compared to the well recognisedproducts of the COX and LOX branches of the AA cascade, the EETs generated by CYPs were only discovered in the early 1980s (Wagner et al., 2011). EETs have various beneficial biological effects, not only do they have antiinflammatory and analgesic actions but they also have protective effects on the cardiovascular system and kidney as recently reported in the literature (Pillarisetti and Khanna, 2012). EETs are metabolized by various pathways, however the main pathway of their metabolism is through conversion to the corresponding 1,2 diols (dihydroxyeicosatrienoates, DHETs), a less bioactive molecular that is characterizes by a pro-inflammatory action. The enzyme that carries out this reaction is the soluble Epoxide Hydrolase (sEH) and its inhibition could stabilize EET levels with expected beneficial biological effects. In the field of veterinary medicine, the first real application of sEHI was conducted in 2013 (Guedes et al., 2013) although some other study had been earlier published (Tsai et al., 2010; Ulu et al., 2012). These molecules have a great potential and their use in veterinary medicine should be tested and developed as soon as possible (in parallel to the human medicine). The final suggestion of this editorial is hence to keep an eye on this new class of molecules that could turn around the pain therapies. 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 (Giorgi, 2012). Treatment of pain and inflammation are important considerations in human medicine. Likewise, in veterinary medicine in recent years, pain has been shown to dramatically affect animal welfare and production and interest in its treatment is increasing (Kim and Giorgi, 2013). Furthermore, veterinary pharmacology still has a reduced drug armamentarium and human drugs are increasingly being investigated for veterinary use. It has only been in recent years that analgesics have been marketed exclusively for veterinary patients. Therefore, it is pivotal that new human drugs and therapies be tested also in veterinary species (Giorgi, 2012). The two main classes of drug used to reduce pain in animals are opioids and Nonsteriodal Anti-Inflammatory Drugs (NSAIDs). Recently, some of the novel molecules in these classes marketed for the human field have been successfully tested on veterinary species (Lavy et al., 2011; Giorgi and Yun, 2012; Giorgi et al., 2012; 2013; Lee et al., 2013; De Vito et al., 2014). In the last few years, many researchers have directed attention towardsarachidonic acid (AA) metabolism and in particular, to the cytochrome P450 (CYP450) enzymes. These have been referred to as the third pathway of AA metabolism, in addition to Cyclooxygenases (COX) and Lipoxygenases (LOX) (Fleming, 2011). All AA metabolites, which encompass theprostanoids, 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 prostanoidsand leukotrienes drive and maintain inflammation, while the anti-inflammatory and analgesic epoxy fatty acids epoxyeicosatrienoic acids (EETs) reduce and resolve inflammation (Wagner et al., 2011). Compared to the well recognisedproducts of the COX and LOX branches of the AA cascade, the EETs generated by CYPs were only discovered in the early 1980s (Wagner et al., 2011). EETs have various beneficial biological effects, not only do they have antiinflammatory and analgesic actions but they also have protective effects on the cardiovascular system and kidney as recently reported in the literature (Pillarisetti and Khanna, 2012). EETs are metabolized by various pathways, however the main pathway of their metabolism is through conversion to the corresponding 1,2 diols (dihydroxyeicosatrienoates, DHETs), a less bioactive molecular that is characterizes by a pro-inflammatory action. The enzyme that carries out this reaction is the soluble Epoxide Hydrolase (sEH) and its inhibition could stabilize EET levels with expected beneficial biological effects. In the field of veterinary medicine, the first real application of sEHI was conducted in 2013 (Guedes et al., 2013) although some other study had been earlier published (Tsai et al., 2010; Ulu et al., 2012). These molecules have a great potential and their use in veterinary medicine should be tested and developed as soon as possible (in parallel to the human medicine). The final suggestion of this editorial is hence to keep an eye on this new class of molecules that could turn around the pain therapies.