A new and efficient synthetic route for the anxiolytic agent CL285032.

CL285032 is an anxiolytic compound currently under investigation as a possible treatment for canine noise phobia associated anxiety. A robust scale-up and manufacturing process is essential for the development and marketability of the drug. The current synthetic route, although reliable, requires seven steps and has a low overall yield (18%), leaving opportunity for improvement. We are presenting an efficient alternative approach toward the synthesis of CL285032 and the results thereof.

Effects of perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine the effects of perzinfotel, butorphanol, and their combination on the minimal alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 7 healthy sexually intact cats (4 males and 3 females), aged 12 to 17 months and weighing 2.8 to 4.6 kg. PROCEDURES: In a crossover design, saline (0.9% NaCl) solution, perzinfotel (2.5 to 15 mg/kg; IV, IM, and SC), butorphanol tartrate (0.2 mg/kg, IM), or a combination of 5 mg of perzinfotel/kg and 2 mg of butorphanol tartrate/kg (both IM) was administered to 6 cats before 7 separate episodes of anesthesia with isoflurane in oxygen. Heart rate, arterial blood pressure, bispectral index (BIS), and inspiration and expiration concentrations of isoflurane were continuously monitored. The isoflurane MAC was determined twice during anesthesia. RESULTS: IV, IM, and SC administration of perzinfotel at 2.5 to 15 mg/kg resulted in a significant decrease in mean isoflurane MAC by 43.3% to 68.0%. The BIS significantly increased after perzinfotel administration via the same routes at 2.5 to 15 mg/kg and after perzinfotel-butorphanol administration IM. Blood pressure was significantly higher after perzinfotel was administered at 5 mg/kg, IM; 10 mg/kg, IV; and 10 mg/kg, SC than after saline solution administration. CONCLUSIONS AND CLINICAL RELEVANCE: Perzinfotel administration decreased the isoflurane MAC and increased several BIS and blood pressure values in anesthetized cats. Administration of perzinfotel prior to isoflurane anesthesia may improve anesthetic safety by reducing inhalant anesthetic requirements and improving cardiovascular function during anesthesia.

Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs when administered as a preanesthetic via various routes or in combination with butorphanol.

OBJECTIVE: To determine the anesthetic-sparing effects of perzinfotel when administered as a preanesthetic via IV, IM, or SC routes or IM in combination with butorphanol. ANIMALS: 6 healthy sexually intact Beagles (4 males and 2 females; age, 18.5 to 31 months; body weight, 9.8 to 12.4 kg). PROCEDURES: After administration of a placebo, perzinfotel (10 to 30 mg/kg), or a perzinfotel-butorphanol combination, anesthesia was induced in dogs with propofol and maintained with isoflurane in oxygen. The following variables were continuously monitored: bispectral index; heart rate; systolic, diastolic, and mean arterial blood pressures; end-tidal concentration of isoflurane; end-tidal partial pressure of CO(2); oxygen saturation as measured by pulse oximetry; rectal temperature; and inspiration and expiration concentrations of isoflurane. A noxious stimulation protocol was used, and the minimum alveolar concentration (MAC) was determined twice during anesthesia. RESULTS: IV, IM, and SC administration of perzinfotel alone decreased the mean isoflurane MAC values by 32% to 44% and significantly increased bispectral index values. A dose of 30 mg of perzinfotel/kg IM resulted in significant increases in heart rate and diastolic arterial blood pressure. The greatest MAC reduction (59%) was obtained with a combination of 20 mg of perzinfotel/kg IM and 0.2 mg of butorphanol/kg IM, whereas administration of butorphanol alone yielded a 15% reduction in the isoflurane MAC. CONCLUSIONS AND CLINICAL RELEVANCE: SC, IM, or IV administration of perzinfotel prior to induction of isoflurane anesthesia improved anesthetic safety by reducing inhalant anesthetic requirements in healthy dogs.

Inability of Short-duration Treatment with a 5-Lipoxy-genase Inhibitor to Reduce Clinical Signs of Canine Atopy.

Abstract- Products of the 5-lipoxygenase metabolic pathway may be important mediators of inflammation in canine skin. Pharmacologic blockade of this pathway may therefore decrease clinical signs associated with canine atopy. To test this hypothesis, 31 dogs were entered on a randomized, double-blind, placebo-controlled, crossover trial to assess the efficacy of an investigational oral 5-lipoxygenase inhibitor (WY-50295) in treating canine atopy. Dogs were treated for 11 days with the drug and 11 days with the placebo, in random order, with a 3-day washout period between the treatment periods. Clinical signs were assessed daily by the owner in all 31 dogs, using a subjective scoring scale. Twelve of the dogs were additionally evaluated at intervals by the investigators and similarly scored. Analysis of variance revealed no significant differences (P > 0.05) in owner or investigator scores assigned during placebo treatment, drug treatment, and no treatment periods. In an end-of-study evaluation, 24.1 per cent of owners reported satisfactory response to placebo capsules and 17.2 per cent reported satisfactory response to the drug, demonstrating a strong placebo effect. Short-duration treatment with WY-50295 did not appear to be effective in reducing clinical signs of atopy.