How to stop cats peeing outside the litter box

Cat Spray No More

Cat Spraying no more is a product that will guide the users on the way to prevent the various mess made by their cats. It is true that a cat that pees in the house can make their home smell like a litter box; it can be upsetting and stressful for the users and can become incredibly expensive if the users are forced to continually clean carpets and floors, or replace furniture. However, Cat Spraying No More is one that will help in the reduction of these problems because it will point the users towards the right things to do and what not to do as regards their cats. This product will stop their cat peeing and spraying outside the litter box for good. This professionally created and proven system will work whether their cat has just started peeing where they should not or if they've been doing it for years. This product is a cheap one that can be learnt by anyone. It comes with certain bonuses that will change the way the users see things as regards cat. They are Cat Training Bible, 101 Recipes for a Healthy Cat, The Cat Care Blueprint, Pet Medical Recorder Software. More here...

Cat Spray No More Summary


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Cat Spray Stop

Susan Westinghouse is the creator of the cat spray stop program. She is an avid veterinarian and cat expert with lots of years of experience. She claims that the guide offers a broad outline and precise approaches targeted at preventing your cat from spraying, despite your cat's stubborn or persistent personality. According to her, it contains the exclusive TTS Taste, Touch, Smell method for pinning the issue, therefore the guide works to stop the cat from spraying and discourages him to ever repeat the bad behavior in the future. It is an e-book that comes with two bonuses attached to it. The first bonus is a nutritional program that will help your cat lose unnecessary weight, while the second bonus is an essential oil recipe for cats that will help to reduce their stress level. This program is suitable for any owner who lives with a cat that has bad litter box habits and often sprays. Susane Westinghouse's guide is characterized by ease of use and it contains a ton of helpful tips that make the process a lot easier both for you and your furry companion. The program is spread across six chapters that take you through a comprehensive tour in how you can solve this annoying problem now, while also learning how to keep it from coming back to haunt you later on in the future. More here...

Cat Spray Stop Summary

Contents: Ebook
Author: Susan Westinghouse
Price: $37.00

Heartworm Clinical Prophylaxis in Dogs and Cats

All MLs are completely efficacious against D. immitis larvae, which allows them to be administered every 30 days. For instance, the oral chewable formulation of ivermectin has been found to be 100 effective in preventing development of D. immitis larvae in dogs and cats when administered 30 or 45 days after challenge with infective larvae (McTier et al., 1992c Paul et al., 1992a). This characteristic provides a safeguard in the case of omission or delay of a monthly treatment, or when the chemoprophylactic history of the dog cannot be verified. Ivermectin and milbemycin oxime have both been found to provide a high degree of protection when administered on a regular basis, beginning 3 months after infection In cats, a more recent study demonstrated that the recommended prophylactic dosage of ivermectin was 66.5 effective in clearing a 7-month-old D. immitis infection that had been transplanted from an infected dog. A dramatic decrease in circulating antigen levels also was detected in...

Effect of Selamectin Against Ectoparasites of Dogs and Cats

At the dose recommended for heartworm prevention in dogs and cats (6 mg kg-1), selamectin is also effective in preventing and controlling cat flea (C.felis) and dog flea infestations (C. canis) (Benchaoui et al, 2000 Boy et al., 2000 McTier et al., 2000b,c,d Shanks et al., 2000a). Selamectin has demonstrated a larvicidal effect on fleas (McTier et al., 2000d) and is also effective for treatment and control of ear mites (Otodectes cynotis) and sarcoptic mange in dogs (Sarcoptes scabiei) (Shanks et al., 2000b,c Six et al., 2000a). In controlled trials using naturally infected dogs and cats, the investigators reported 100 efficacy against O. cynotis following a single treatment with selamectin (Shanks et al., 2000c). Against S. scabiei and in clinical trials against O. cynotis, the investigators reported that two monthly treatments were needed to obtain clinical and parasitological cure (Shanks et al., 2000b Six et al., 2000a). Complete efficacy for the recommended dose of selamectin...

Distribution and Cellular Localization of NOS in the Central Nervous System

As well as processes from local circuit neurons (35). However, some staining may arise from primary afferents at least at the thoracic and lumbar levels (39). In other species, such as cats and humans, the contribution from primary afferents to neuropil staining in the dorsal horn might be more substantial (36,40). As mentioned in the previous section, after biochemical analysis both a soluble and a membrane-bound insoluble fraction of NOS were found in the brain. We have recently demonstrated that the use of different tetrazolium salts for the histochem-ical localization of NADPH-d yields different subcellular localization of positive reaction sites (41) (Fig. 4). When observed in the electron microscope, nitroblue tetrazolium (NBT) formazan deposits were scattered throughout the neuronal cell body and processes without any preferential association with cell organelles. In keeping, those who have used NOS immunocytochemistry have not been able to observe a specific association with...

Basic Pharmacology Introduction

Some pharmacokinetic studies have been published on avermectins in livestock animals, mostly after pour-on or subcutaneous administration (Ali and Hennessy, 1996 Oukessou et al, 1996,1999 Shoop et al, 1996 Toutain et al, 1997 Gayrard et al, 1999 Lifschitz et al, 1999 Perez et al, 1999 Atta and Abo-Shihada, 2000). However, concerning milbemycins, other than the work performed at Sankyo Co. which has been published in Ide et al. (1993), little information has become available about their pharmacokinetics and metabolism in dogs and cats (after oral or i.v. administration). On the

Polysaccharide incorporation

Circulation time of51 Cr labeled artificial rbc (mean diameter, 5 ) after intravenous infusion into cats arterial sampling. Upper line sulfonated nylon membrane artificial rbc's. Lower line nylon membrane artificial rbc's. Survival estimated as percentage of radioactivity. (From Chang, 1965,1972a.) Fig. 5.7. Circulation time of51 Cr labeled artificial rbc (mean diameter, 5 ) after intravenous infusion into cats arterial sampling. Upper line sulfonated nylon membrane artificial rbc's. Lower line nylon membrane artificial rbc's. Survival estimated as percentage of radioactivity. (From Chang, 1965,1972a.)

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The inconsistencies in the effects of catnip could be attributed to a few possible causes. As Sherry and Hunter illustrated (1979), the effects could be biphasic and thus dose dependent. Another possibility is interspecies differences. A more dramatic illustration of this is in the reaction that cats have to catnip (Siegel 1989). Cats will sniff, lick, and chew the leaves of the plant, followed by short periods of blank staring into space and shaking the head from side to side. Next they will rub their body against the plant and some fall over and roll in it. When introduced to catnip, cats will later return to the site where they encountered it. These behaviors indicate a pleasurable state, and both male and females may adopt mating postures with erections occurring in the males. Nepetalactones are believed to mimic a scent in cat urine that triggers sexual behaviors. The sexual nature of the feline response to catnip is suggestive of pheromonal activity at the vomeronasal organ...

Taurine Generalized Distribution Intraretinal Localization

The major pathway for the biosynthesis of taurine in mammalian tissues, particularly liver and brain, is via cysteine sulphinic acid decarboxylase (CSD), a vitamin B6-dependent enzyme that catalyzes the conversion of cysteine sulphinic acid to hypotaurine (7). Hypotaurine is then converted to taurine in a reaction catalyzed by hypotaurine oxidase. In the livers of cats, monkey and man, although the synthetic pathway is present, taurine biosynthesis is limited by low activity of CSD. In fact, human levels of CSD are particularly low, about a tenth of that in the cat (1). The synthetic pathway has also been shown to be present in the retinas of various species (8,9). Despite this presence, the activity of CSD is considerably low, requiring blood-borne import of the amino acid to maintain the high levels of retinal taurine.

Fluid Movement In The Brain

In the tissue of the CNS, under normal conditions, fluid flows within the gray matter are negligible flows can be significant within white matter. For example, flows of 10 pm min were measured in white matter, but not gray matter, in the periventricular tissue of cats 17 . This extracellular fluid (ECF) flow, which moves towards the ventricular surface, is presumably the result of fluid leakage from the capillaries that moves predominantly through white matter tracts.

Similarity Searching with Pharmacophore Fingerprints Some Examples

Eventually, the ultimate judge of molecular descriptors is not being the best in benchmarking but having practically contributed to the discovery of new compounds. Logically, 2D pharmacophore fingerprints were typically employed as quick and effective means to perform scaffold hopping32,63,64 and or bio-isosteric replacements65 in virtual screening or de novo drug design.66 A typical similarity screening example42 based on CATS is depicted in Figure 2.1. The two isofunctional compounds (T-channel blockers) both feature the same global pharmacophore pattern two aromatic systems (one including some polar groups) separated by a flexible aminodialkyl linker. Although there is significant variance within the aromatic terminal groups, the overall pharmacophore pattern - and the activity - was conserved. Notably, however, chemotypes with flexible linkers spanning two rigid ends are most likely to perform well in topological pharmacophore-based similarity screening. These fingerprints would...

Combinatorial Evolutionary Design of Drug Like Molecules

Ordering of molecular building blocks based on the Tanimoto similarity (upper row) and the CATS distance (lower row) to benzamidine. For small fragments there is no drastic difference in ranking resulting from either Tanimoto or topological pharmacophore similarity. Significantly different orderings are observable only for larger structures.

Penicillin as a Focal Epileptogenic Agent

Penicillin has been widely used to produce seizures in rats and cats. Currently, penicillin is usually employed parenterally in high doses to produce seizures.2829 When used parenterally, the dose is very high, generally in the order of 1.2 million units per kilogram in the rat.29 On the other hand, when penicillin is applied directly to the cortex, much lower quantities are required.

Principal subcortical afferents

(1990) detected high levels of Glu in morphologically identified retinal terminals in the lateral geniculate nucleus of monkeys and cats. In the ventrobasal complex, enrichment of Glu has been detected in sensory afferent terminals identified either by morphological criteria (Hamori et al., 1990) or by anterograde transport (cervicothalamic tract Broman and Ottersen, 1992 afferents from the dorsal column nuclei De Biasi et al., 1994a). Spinothalamic tract terminals in the cat nucleus submedius (Ericson et al., 1995) and in the posterior thalamic region of monkeys (Blomqvist et al., 1996) are similarly enriched in Glu. Enrichment of Glu has also been detected in cerebellothalamic terminals in the ventromedial and ventrolateral nuclei (Schwarz and Schmitz, 1997). In all studies in which both sensory afferent terminals and terminals of presumed cortical origin have been examined, the levels of Glu are higher in the corticothalamic than in the sensory afferent terminals. The higher...

Localization of Delta Opioid Receptor Immunoreactivity

The presence of preprodynorphin- and preproenkephalin-derived pep-tides in enteric neurons has been detected by immunohistochemical methods as well. The distribution of the enkephalins is of particular interest as these peptides are thought to be a class of endogenous ligands for delta opioid receptors 31 . Indeed, they bind preferentially to the cloned delta opioid receptor relative to the other recombinant opioid receptor types 32 . Enkepha-linlike immunoreactivity is present in neurons both intrinsic and extrinsic to the intestinal wall and is localized in nerve fibers along the entire length of the digestive tract, from esophagus to colon, in a wide variety of species including rats, guinea pigs, hamsters, cats, pigs, and humans 33-39 . In general, enkephalin-immunoreactive neurons are present in myenteric ganglia, but are rare or absent in submucosal ganglia. Unfortunately, there have been no reports of the anatomical interrelationships between enkephalinergic nerves and...

Cultural and political trends

Although it may be extreme, it is not inaccurate to assert that companion animals have become surrogate children for many people in CSI countries. Animal health companies have recognized lately that pet owners will spend a great deal of money on veterinary medicines, including anthelmintics, for dogs, cats and horses. The emotional investment in companion animals drives consumers to pay a premium for value-added products. Currently, spectrum of action, coupled with persistence, is the gold standard set by the MLs for anthelmintics endectocides. However, one can envisage the development of an upscale veterinary medical market based on perceived (due to advertisement) value of high-cost products, one that is less driven by efficacy than by social status (as has developed in, for instance, children's clothing or dog and cat food).

Chemoprophylactic Treatment of Feline Heartworm Disease and its Effect on Internal Parasites

Heartworm preventive treatment in cats follows the same regimen established for dogs, that is, monthly dosing should begin within 1 month from the start of the transmission season and the last dose should be given within 1 month from the end of the risk period. Ivermectin is marketed in the USA for use as a prophylactic agent in cats given monthly at the dose of 24 g kg-1 (McTier et al, 1992c Paul et al, 1992b). This oral dosage is also highly effective for treatment and control of A. tubaeforme (94.5 ) and A. braziliense (98.5 ) (Robertson et al, 1992). Nolan et al. (1992) reported 92.8 efficacy against adult A. braziliense and 90.7 against adult A. tubaeforme. The effect of ivermectin on microfilaraemic cats was studied recently. Each of 20 cats was experimentally infected with four pairs of adult male and female heartworms. Ten cats were treated with ivermectin and ten remained untreated as controls. Nineteen of the 20 cats became microfilaraemic, and three of the ten control cats...

O Factors Affecting Drug Metabolism

Factors Affecting Drug Metabolism

Species differences in many conjugation reactions also have been observed. Often, these differences are caused by the presence or absence of transferase enzymes involved in the conjugative process. For example, cats lack glu-curonyltransferase enzymes and, therefore, tend to conjugate phenolic xenobiotics by sulfation instead.497 In pigs, the situation is reversed pigs are not able to conjugate phenols with sulfate (because of lack of sulfotransferase enzymes) but appear to have good glucuronidation capability.497 The conjugation of aromatic acids with amino acids (e.g., glycine, glutamine) depends on the animal species as well as on the substrate. For example, glycine conjugation is a common conjugation pathway for benzoic acid in many animals. In certain birds (e.g., duck, goose, turkey), however, glycine

Activitydependent Regulation Of Naag Expression

I examined NAAG immunoreactivity in the retina and LGN of monocularly deprived (MD) cats and compared it with that in normal cats.51, 52 As noted above, in the LGN of the normal cat, both the neuropil and the somata of relay cells are heavily labeled. Long-term monocular deprivation decreases labeling of the somata, but not the neuropil, in the deprived layers of the LGN (Fig. 5). There is little or no loss of label in the retinal ganglion cells of the deprived eye, as might be expected, given that the labeling of their terminals in the LGN is also unchanged. There is also no change in immunoreactivity for GAD, which is found in the interneurons of the LGN. The changes in NAAG immunoreactivity of the LGN neurons in MD cats are much more striking than changes demonstrated with immunocytochemistry for glutamate, cytochrome oxidase histochemistry or uptake and incorporation into protein of 3H-leucine. Thus, the changes are unlikely to be due to an overall decrease in metabolism or...

Target animal safety

For both dogs (Novotny et al., 2000) and cats (Krautmann et al., 2000), drug tolerance and margin of safety were evaluated together in a single study. For each species, selamectin in the commercial formulation was applied topically at the base of the neck. Unit doses of 0,1, 3, 5, or 10x (0, 6, 18, 30 or 60 mg kg-1, respectively) the recommended dose were administered once every 28 days for seven treatments to 6-week-old puppies or kittens. No adverse effects were observed clinically or histopathologically in either study. For cats (6-week-old), a second study (Krautmann et al., 2000) was conducted using exact doses of 0, 16, 48 or 80 mg kg-1 of selamectin in a prototype 8 formulation applied topically to the base of the neck weekly for four treatments. No adverse effects were seen in the selamectin-treated animals. Oral safety was evaluated in both dogs (Novotny et al., 2000) and cats (Krautmann et al., 2000). In each case, animals 5 months of age were treated per os with saline or...

General Methodologies Utilized

With rats and gerbils predominating.183839 Other species, including cats and primates, are also used in epilepsy studies.40 When the specific animal model is chosen, the animals are acquired and allowed to acclimate to the housing conditions. As mentioned earlier, the housing conditions must remain constant throughout any experiment that attempts to investigate rhythmic processes. If a rhythm in seizure severity

Small and Large Intestine

As in the small intestine, delta opioid receptors may mediate a portion of the antimotility effects of opioids on the colon. For example, delta opioid agonists such as DADLE, DSLET, and DPDPE delay colonic transit in cats and rabbits 102,103 . In the human colon, the enkephalins and their derivatives DADLE and DPDPE decrease the amplitude of inhibitory junction potentials in circular smooth muscle 104 . This finding may indicate that these agonists act on presynaptic delta opioid receptors to reduce inhibitory neurotransmission to colonic myocytes. A similar effect of DPDPE on inhibitory junction potentials was observed in the guinea pig colon which was attributed to a decrease in N-type calcium conductance in inhibitory nerve terminals 105 . Smooth muscle contractions induced by electrical field stimulation are inhibited by delta opioid agonists in the large intestines of humans 106,107 , cats 108 , guinea pigs 107 , rats 109,110 , and mice 110 . Neurogenic contractions of the feline...

Human And Animal Health Crossover

Injectable products are generally good dosage forms for (almost) direct transition to use in animals. If dosing volumes are acceptable for the animals being treated, the direct use in animals can be pursued. Immediate-release tablets appear attractive candidates, but might prove difficult, particularly if there are palatability issues with the product. This can be overcome by instructions for pushed administration down the animal's throat or to hiding it in food or treats. Even so, it should be realized that the shorter gastrointestinal tract transit time for dogs and cats could result in inadequate absorption. Also, in both cases (injectables or oral immediate-release tablets) there may be different extents of drug metabolism or different drug absorption mechanisms in animals compared with that in humans so these aspects need to be considered and examined. A good understanding of pharmacokinetic parameters in the different species is important when attempting to cross over human...

Topological Fingerprints

CATS48 (chemically advanced template search) specifically targets the problem of scaffold hopping. It is based on the idea of generating an exhaustive molecular 2D fingerprint based on topological pharmacophore models for pair-wise comparison of molecules. CATS3D81 is the three-dimensional, computationally more demanding counterpart of CATS. It is based on the correlation vector representation of a 3D conformation - in contrast to the topological representation of CATS - and has been successfully applied to identifying inhibitors of metabotropic glutamate receptors (mGluR) 1 and 5, using both supervised and unsupervised neural networks.183 As ligand binding to the protein is a 3D problem, the exploitation of this additional information in CATS3D is supposed to increase predictive accuracy. SURFCATS81 is another extension of CATS3D, considering molecular surfaces.

Machinelearning of Topological Pharmacophores from Fingerprints

Individuals will be assigned to the category that is most similar in terms of its characteristic fingerprint. Since these characteristic fingerprints evolve during the training step, their final states may be thought as consensus fingerprints of the individuals in each category. As training is completely unbiased with respect to the properties of the objects to be categorized, the utility of a SOM only becomes apparent after it has been built if objects sharing a certain property are assigned to a same neuron (more often than randomly expectable) then it may be assumed that any external objects assigned to that neuron are likely to share that property as well. To resume, a topological pharmacophore fingerprint-driven SOM performs a similarity-based screening operation, except that the known actives are not used straight ahead as queries but are first classified, together with the inactives, into phar-macophore pattern categories. The resulting categories...

What Species Have Audiogenic Seizures

Experimental seizure models in laboratory animals have played a prominent role in epilepsy research over the years. Among these models are those that utilize the placement of metals to the brains of animals to produce seizures. The species most often employed have been monkeys, cats, or rats, although other species have also been studied. An advantage of metals over many other substances, such as organic chemicals, is that metals tend not to be absorbed by the body, and not to be changed by metabolism and or other chemical reactions. Therefore, they tend not to diffuse from the area of injection and to persist at the site of implantation or administration for at least several days or weeks. A large number of metals, as well as other substances, have been shown to produce seizures when applied directly to the brains of experimental animals. The first such report was by Kopeloff et al.1 They observed that application of alumina cream to the cerebral cortex of monkeys resulted in the...

Hydrogen Peroxide Production Associated with Photosynthesis

Photorespiratory C02 loss would be much higher if catalase were not effective in preventing chemical decarboxylation of keto-acids such as glycoxylate and hydroxypyruvate in the peroxisome.5 Three unlinked structural catalase genes (Catl, Cat2, and Cat3f' have been found in C3 plants (such as Nicotiana plumbaginifolia) and in C4 plants (such as maize). These genes encode biochemically distinct catalase isoenzymes (CAT-1, CAT-2, and CATS). Two of these are expressed in mature tobacco leaves. CAT-1 comprises about 80 of the leaf catalase activity and is considered to fulfil the role of H202-scavenging during photorespiration while CAT-2 accounts for the remaining 20 and is localized in the phloem.46 Transformed tobacco lines deficient in either CAT-1 or CAT-2 (or both) develop necrotic lesions on their leaves when exposed to high light because the production of H2Oz through photorespiration is increased in these conditions.5,6'40 Similarly, catalase deficiency in barley was lethal when...

Chapter Three

Oleamide (cis-9-octadecenamide) is the prototype long chain primary fatty acid amide lipid messenger. The natural occurrence of oleamide was first reported in human serum in 1989. Subsequently oleamide was shown to accumulate in the cerebrospinal fluid of sleep-deprived cats and to induce sleep when administered to experimental animals. Accordingly, oleamide first became known for its potential role in the mechanisms that mediate the drive to sleep. Oleamide also has profound effects on thermoregulation and acts as an analgesic in several models of experimental pain. Although these important pharmacologic effects are well establish, the biochemical mechanism for the synthesis of oleamide has not yet been defined. This chapter reviews the biosynthetic pathways that have been proposed and highlights two mechanisms which are most supported by experimental evidence the generation of oleamide from oleoylglycine by the


The natural occurrence of oleamide was first reported in human serum in 1989 (Arafat et al., 1989). Subsequently oleamide was shown to accumulate in the cerebrospinal fluid of sleep-deprived cats (Cravatt et al., 1995) and to produce sleep when administered to experimental animals (Cravatt et al., 1995 Mendelson and Basile, 2001). Accordingly, oleamide first became known for its potential role in the mechanisms that mediate the drive to sleep. Oleamide also has profound effects on thermoregulation and locomotion (Basile et al., 1999 Chaturvedi et al., 2006 Fedorova et al., 2001 Huitron-Resendiz et al., 2001 Lichtman et al., 2002 Martinez-Gonzalez et al., 2004 Murillo-Rodriguez et al., 2001) and produces antinociception, or analgesia, in models of experimental pain (Fedorova et al., 2001). Although these pharmacologic effects are well established, the underlying mechanisms involved are not understood.


Selamectin is a semisynthetic monosaccharide oxime derivative of doramectin that was identified from a targeted effort to identify a macrocyclic lactone that retained efficacy against heartworms consistent with existing products from the class, while providing utility against fleas at a dose safe for use in dogs and cats (Banks et al., 2000 Bishop et al., 2000). Monosaccharide derivatives and, most notably, their C-5 oximes showed flea activity, with selamectin emerging as the best compound from the targeted screening effort. Selamectin is a white powder and its structure is provided in Fig. 1.2.3. The chemical name for selamectin is Bja, its molecular formula is C H NOn and its molecular weight is 770. Revolution is the commercial name everywhere, except for Europe, where the name is Stronghold . The commercial product comes as a ready-to-use, topical 6 or 12 solution of selamectin in an isopropyl alcohol dipropylene glycol methyl-ether vehicle. Based on commercial tube size and...


The topical formulation of selamectin is licensed for use in dogs and cats of 6 weeks or older in various countries. Selamectin administered as a single topical dose at 24 mg kg-1 (four times the minimum commercial dose) to dogs or cats in an isopropyl alcohol butylated hydroxytoluene + dipropylene glycol monomethyl-ether vehicle provided a Cmax of 86.5 34.0 ng ml-1 at 72 48 h post-treatment and an AUC of 15,229 4078 (ng ml-1) x h in dogs and a Cmax of 5513 2173 ng ml-1 at 15 12 h post-treatment and an AUC of 743,349 443,430 (ng ml-1) x h in cats. In contrast, oral administration of selamectin at a dose of 24 mg kg-1 in a sesame-seed oil vehicle achieved a Cmax of 7630 3140 ng ml-1 at 8 5 h post-treatment with an AUC of 227,901 121,866 (ng ml-1) x h in dogs, and a Cmax of 11,929 5922 ng ml-1 at 7 6 h post-treatment with an AUC of 1,109,933 726,616 (ng ml-1) x h. There was a mean systemic availability of selamectin in dogs from the topical and oral doses of 4 (range 3-7 ) and 62 (range...

Case 6 GsK3

To find new chemotypes for GSK-3 inhibition, a high-throughput screening exercise was carried out using the Novo Nordisk compound collection and screening them against GSK-3. Although this HTS campaign produced 47 hits, it was determined that only a few were suitable for follow-up optimization. To find better leads, the authors used a computational chemistry approach for scaffold hopping. Using CATS2, a customized version of the original CATS (Chemical Advanced Tempalte Search) methodology, the authors compared 32 virtual libraries against the 47 hits found in the HTS campaign. Here, one of the virtual libraries stood out from the rest with a high hit rate ( 800 virtual compounds). Using a fragment-based, two-dimensional fingerprint diversity analysis approach, the hits were distilled down to a total of 324 hits. This approach took lead 275 into scaffold 276.


The prevalence and distribution of heartworm infections in dogs are better described than for other animal species, but gradually more information on the frequency of diagnosis of infection in cats is becoming available. It is now generally accepted that heartworm disease occurs in cats in any area where dogs are infected (Guerrero et al., 1992a McCall et al., 1994), but the geographical distribution and level of infection are less predictable in cats than in dogs. In highly endemic areas with sufficient rainfall, essentially every unprotected dog becomes infected (McTier et al., 1992b). In contrast, about 75 of cats can be infected experimentally with D. immitis L3 (McCall et al, 1992a). However, the prevalence of natural infections in cats is between 5 and 20 that for dogs in the same geographical area (Ryan and Newcomb, 1995). Outdoor cats and strays who are seemingly exposed to high numbers of bites from infective mosquitoes may be able to mount an effective immune response that...


D. immitis infections in dogs and cats have been described in all continents. What was considered to be a regional problem of dogs in the USA is now a national problem that is considered to be endemic in 49 states of the Union, with no clearly documented cases in Alaska however, focal transmission appears to be possible in all 50 US states. Growing prevalence has also been described in Mexico, Puerto Rico and the Caribbean (Genchi et al., 2001). Heartworm infections in cats are now being reported by veterinarians with increasing frequency in the USA and southern Canada (Guerrero et al., 1992c Robertson-Plouch et al., 1998). The prevalence for heartworm infections in dogs in South America has been reviewed previously by Guerrero et al. (1992b), while infections in cats have only been reported by Labarthe et al. (1997). Heartworm disease in dogs and cats is well established in Australia (Kendall et al., 1991) and in Japan (Guerrero et al., 1992a Roncalli et al., 1998). The prevalence...

The Patient

Poultry, together with fish and any other animal from which meat or other products such as eggs or milk are obtained. Companion animals are those that are considered pets and include dogs, cats, and horses. Birds, lizards, rabbits, etc. can be considered companion animals however, they are sometimes classified as exotic animals. Because the latter species represent only a small proportion of the companion animal market, dosage forms that have been developed for the more common species (e.g., dogs and cats), or indeed, for humans, are often adapted for use in the exotic species since the markets are not usually large enough to warrant development of such specialized products.

Key Challenges

The end user can often successfully deal with solutions or suspensions that contain the same amount per volume and which can be administered at different volumes for different-sized animals. However, these liquid products are sometimes not so easy to transfer across species, as palatability becomes an issue. For example, cats are known to lack a gene allowing them to taste sugar sweets, so a sweet formulation for dogs will not gain the same acceptance in cats. Solid dosage forms can be challenging as a wide range of dosing amounts are often needed between species, and administering a handful of tablets to a large dog may not be a viable option. One feasible alternative is to consider developing single- or double-scoring tablets. For farmed animals, a solution is to develop a flexible product that can be produced in different sizes during the manufacturing process. The TimeCapsule (Fig. 1) achieves this through its simple formulation approach and flexible manufacturing process. While...


Compared to human platelets, the functional responses of animal platelets to TP receptor agonists are quite varied. Platelets from some species, such as cats, guinea pigs and rabbits, were reported to aggregate irreversibly when stirred with sodium arachidonate or 9,11-azo-PGHj, while sheep and dog platelets failed to aggregate under the same conditions (74,172). Horse platelets aggregated reversibly in response to arachidonate


Other species, including mice, pigs, goats, cows, cats, sheep, and several endangered animals, have been cloned with similar techniques. Even at its most successful, reproductive cloning is a very delicate process (Dolly was the single success out of 176 attempts). The cloned animals tend to have higher than average birth weight and some unexplained health problems. There have been several reports of cloned animals having shorter lifespans than their naturally produced siblings. Humans have not been cloned in this way, and there is evolving legislation and scientific ethical guidelines against doing this however, there have been reports of failed human reproductive cloning experiments conducted in developing countries.

Similarity Search

Schneider et al. have developed a special technique for performing virtual screening referred to as Chemically Advanced Template Search (CATS).257 Within its framework, chemical structures are described by means of so-called correlation vectors, each component of which is equal to the occurrence of a given atom pair divided by the total number of non-hydrogen atoms in it. Each atom in the atom pair is specified as belonging to one of five classes (hydrogen-bond donor, hydrogen-bond acceptor, positively charged, negatively charged, and lipophilic), while topological distances of up to ten bonds are also considered in the atom-pair specification. In ref. 257, the similarity is assessed by Euclidean distance between the corresponding correlation vectors. CATS has been shown to outperform the MERLIN program with Daylight fingerprints251 for retrieving thrombin inhibitors in a virtual screening experiment.257


Because animals cannot self-administer, tablets as a single-unit dosage form are used less often in veterinary medicine compared with human medicine. However, they are still a prevalent dosage form. Tablets are used in a wide variety of indications, with several species, are available in a large size range, and are manufactured by several different processes. The primary species treated with tablets are dogs and cats however, for some indications, cattle and sheep may receive a large tablet (often referred to as a bolus). The major indications for tablets in dogs and cats would be those diseases that mirror those seen in humans. These would include the therapeutic areas of anticonvulsants, anti-inflammatories, antimicrobials, antitussives (there is a treatment for coughing dogs), antispasmodics (there is a treatment for cats with upset stomachs diarrhea), behavior modification (e.g., separation anxiety in dogs), cardiovascular, diuretics, thyroid hormone replacement, laxatives, muscle...


In the rat, the 5-opioid agonist D-Ala2 deltorphin II does not alter gastric emptying after its peripheral or central administration 80 . In cats however, DPDPE reduces gastric contractions induced by vagal stimulation, and its effect is prevented by the 5-opioid antagonist ICI-174,864 86 . In dogs, a role for 5-opioid receptors in the regulation of smooth muscle contractility in the gastric fundus and antrum is not well defined. On the one hand, DPDPE has no effect on gastric smooth muscle relaxation in response to feeding after its peripheral (IV) or central (ICV) administration, whereas morphine and DAMGO enhance gastric relaxation in this paradigm 87 . On the other hand, contractions of the gastric antrum are increased by the addition of the delta opioid receptor-selective antagonist ICI174,864, suggesting that endogenous opioids are released in this tissue and stimulate 5-opioid receptors to depress antral contractions 88 . In addition, delta opioid agonists inhibit contractions...

Background History

In the coronary venous blood of dogs and cats in 1933 12 . Acetylcholine effects on muscle were nicotine-sensitive, its cardiovascular effects were not 13 . Dale proposed a division of autonomic pharmacology into cholinergic and adrenergic domains (he invented these words). John Eccles elevated Dale's principle to a formal theory of neurotransmission later, in the 1950s, after intracellular recording demonstrated a chemical basis for CNS neurotransmission. Dale himself never ruled out multiple transmitters. After observing atropine-resistant effects of vagus nerve stimulation, he said Figure 5. This figure, modified from Haefely 42 and reproduced with permission, shows blood pressure responses to three different treatments in cats treated with two false transmitter precursors (amethyl dopa and a-methyl meta tyrosine) and reserpine. DMPP (dimethyl phenylpiperazinium), a nicotinic ganglionic stimulant tyramine, an indirect acting sympathomimetic drug and NA, the natural transmitter,...

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