A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function, is being under development by Merz Pharmaceuticals GmbH. It is a selective non-competitive mGlu1 receptor antagonist (IC50: 10 nM); showing 34-fold selectivity over mGluR5 and no significant activity at other mGluR receptors, neurotransmitter receptors, ion channels, and transporters. A-841720 demonstrated full efficacy in various in vivo animal pain models.

Dermorphin is a selective mu-opioid receptor agonist. It was isolated from isolated from skin extracts of frogs belonging to the genus Phyllomedusa and was shown to relife pain in patients with postoperative pain syndrome.

CHOLINE is a basic constituent of lecithin that is found in many plants and animal organs. Choline was officially recognized as an essential nutrient by the Institute of Medicine in 1998.1 Its role in the body is complex. It is needed for neurotransmitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), lipid transport (lipoproteins), and methyl-group metabolism (homocysteine reduction). It is the major dietary source of methyl groups via the synthesis of S-adenosylmethionine (AdoMet). At least 50 AdoMet-dependent reactions have been identified in mammals, and it is likely that the number is much higher. Choline is required to make the phospholipids phosphatidylcholine, lysophosphatidylcholine, choline plasmalogen, and sphingomyelin—essential components for all membranes. It plays important roles in brain and memory development in the fetus and appears to decrease the risk of the development of neural tube defects. The importance of choline in the diet extends into adulthood and old age. In a study of healthy adult subjects deprived of dietary choline, 77% of the men and 80% of the postmenopausal women developed signs of subclinical organ dysfunction (fatty liver or muscle damage). Less than half of premenopausal women developed such signs. Ten percent of the subjects studied developed fatty liver, muscle damage, or both when they consumed the Adequate Intake (AI) of choline. The damage was reversed when they consumed a high-choline diet. Plasma choline concentration has been found to vary in response to diet, decreasing approximately 30 percent in humans fed a choline-deficient diet for 3 weeks. Based on estimated dietary intakes and studies reporting liver damage with lower choline intakes, the Institute of Medicine, Food and Nutrition Board set the AI for choline at 425 milligrams/per day for women aged 19 and older, and 550 milligrams/per day for men aged 19 and older.

Carprofen is an anti-inflammatory drug developed in Japan by Nippon Roche Research Center. Carprofen, as many NSAIDs, selectively inhibits COX-2 and was shown to suppress inflammation in vitro, using osteoarthritis models. The drug was approved by FDA for human use under the name Ridamyl, however, now it is sold only for veterinary purposes and prescribed for the treatment of postoperative pain and the relief of pain and inflammation associated with osteoarthritis in dogs.

Robenacoxib (trade name Onsior) is a non-steroidal anti-inflammatory drug (NSAID) used in veterinary medicine for the relief of pain and inflammation in cats and dogs. In an inflammation model in cats, Robenacoxib had analgesic, anti-inflammatory and antipyretic actions with a rapid onset of action (0.5 h). In an in vitro whole blood assay in cats, Robenacoxib demonstrated selective COX-2 inhibition. After oral administration of robenacoxib tablets at 1 mg/kg without food, peak blood concentrations are attained rapidly with a median Tmax of 0.5 h, a mean Cmax of 1159 ng/ml and a mean AUC of 1337 ng*h/ml. Robenacoxib persists longer in the inflammatory exudate of a tissue cage model than in blood. The median Robenacoxib elimination half-life in exudate was about 27 hours versus 2.5 hours for blood. Robenacoxib is extensively metabolized by the liver in cats. The systemic exposure of lactam metabolite is about 25% of Robenacoxib exposure following oral administration to fed cats. Further, the systemic exposure to lactam appears to be two-fold greater in fed cats than fasted cats. Apart from one lactam metabolite, the identity of other metabolites is not known in cats.

Firocoxib is a selective COX-2 inhibitor which was approved by FDA and EMEA for the treatment of osteoarthritis and postoperative pain in dogs (Previcox trade name) and horses (Equioxx trade name). The drug is not for human use.

Borneol, a monoterpenoid alcohol, is a component of many essential oils. Barneol occurs in nature as a single enantiomer (d- or l-, depending on the oil type) or, less frequently, as the racemate. Several studies have proved the effectiveness of borneol. In Chinese medicines borneol has been used in relieving symptoms of anxiety, fatigue and insomnia; inducing anesthesia and analgesia to alleviate abdominal pain, wounds and burns; relieving rheumatic pain, hemorrhoids, skin diseases and ulcerations of the mouth, ears, eyes or nose; to treat sore throats and skin infections, and is mainly used to treat cardiovascular and cerebrovascular diseases. Borneol has a significant therapeutic effect on neuralgia. This compound is considered a GRAS approved by the FDA as food flavor. Additionally, borneol is a fragrance ingredient. GABAA, TRPV3, TRPM8 and TRPA1 have been identified as the molecular targets of borneol.

Meptazinol is a unique opioid analgesic. Binding studies suggest a relative selectivity for mu-1 opioid receptor sites. Meptid is indicated for the treatment of moderate to severe pain, including post-operative pain, obstetric pain and the pain of renal colic. The most commonly reported adverse reactions after treatment with meptazinol are nausea, vomiting, dizziness, diarrhoea and increased sweating, constipation, abdominal pain, rash, vertigo, headache, drowsiness, somnolence and dyspepsia.

Lappaconitine is an alkaloid isolated from the root of Aconltitum sinomantanum Nakai. It has a strong analgesic activity that does not involve the opioid receptor. It was shown to have class-I antiarrhythmic action and irreversibly blocks cloned human heart (hH1) channels by binding to the site 2 receptor.

Chloral hydrate was discovered in 1832, and was used as a sedative in late 19th century. Chloral hydrate has not been approved by the FDA or the EMA, and is on the list of unapproved drugs that are prescribed for postoperative pain control, sedation and to prevent alcohol withdrawal and reduce anxiety associated with withdrawal of opiates or barbiturates. Mechanism of action of chloral hydrate is not known. It is generally believed that the central depressant effects are due to the principal pharmacologically active metabolite trichloroethanol, which has a plasma half- life of 8 to 10 hours, and acts by potentiating GABA-activated Cl currents.