Effect of combinations of morphine, dexmedetomidine and maropitant on the electroencephalogram in response to acute electrical stimulation in anaesthetized dogs.

This study was conducted to compare the efficacy of combinations of morphine, dexmedetomidine and maropitant in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetized dogs subjected to a noxious electrical stimulus. In a crossover study, eight healthy adult dogs were randomly allocated to four groups: Mor: morphine 0.6 mg/kg; Dex + Mor: morphine 0.3 mg/kg + dexmedetomidine 5 µg/kg; Maro + Mor: morphine 0.3 mg/kg + maropitant 1 mg/kg; and Dex + Maro + Mor: morphine 0.2 mg/kg + dexmedetomidine 3 µg/kg + maropitant 0.7 mg/kg. Following intramuscular administration of test drugs in a minimal anaesthesia model, a supramaximal electrical stimulus (50 V at 50 Hz for 2 s) was applied and the EEG data were recorded. There were significant increases (p < .05) in the poststimulus median frequency (F50) only in groups Mor and Maro + Mor. Dex + Mor group had a significantly lower change in F50 and F95 compared to all other treatment groups. There was no correlation of the changes in EEG frequencies with blood plasma concentration of the drugs during and after noxious stimulation. Combination of dexmedetomidine and morphine was most effective in abolishing the changes in EEG indices in response to a noxious stimulus indicating a supra-additive interaction between these two drugs.

Pharmacokinetics of morphine in combination with dexmedetomidine and maropitant following intramuscular injection in dogs anaesthetized with halothane.

The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia. Eight healthy dogs weighing 25.76 ± 3.16 kg and 3.87 ± 1.64 years of age were used in a crossover study. Dogs were randomly allocated to four groups: (1) morphine 0.6 mg/kg; (2) morphine 0.3 mg/kg + dexmedetomidine 5 µg/kg; (3) morphine 0.3 mg/kg + maropitant 1 mg/kg; (4) morphine 0.2 mg/kg + dexmedetomidine 3 µg/kg + maropitant 0.7 mg/kg. Blood samples were collected before, 15 and 30 min, and 1, 2, 3 4, 6 and 8 hr after injection of the test drugs. Plasma concentration of the drugs was determined by liquid chromatography-mass spectrometry. The elimination half-life (T1/2 ) of morphine was higher and the clearance rate (CL) was lower when combined with dexmedetomidine (T1/2  = 77.72 ± 20.27 min, CL = 119.41 ± 23.34 ml kg-1  min-1 ) compared to maropitant (T1/2  = 52.73 min ± 13.823 ml kg-1  min-1 , CL = 178.57 ± 70.55) or morphine alone at higher doses (T1/2  = 50.53 ± 12.55 min, CL = 187.24 ± 34.45 ml kg-1  min-1 ). Combining morphine with dexmedetomidine may increase the dosing interval of morphine and may have a clinical advantage.

Evaluation of analgesic interaction between morphine, dexmedetomidine and maropitant using hot-plate and tail-flick tests in rats.

OBJECTIVE: To determine if the combinations of morphine, dexmedetomidine and maropitant enhance the analgesic effect and decrease the dose of individual drugs in rats subjected to noxious thermal stimulation with hot-plate and tail-flick tests. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: A total of 96 male Sprague-Dawley rats. METHODS: The rats were randomly assigned to the following groups: 1) morphine (3 mg kg-1; Mor); 2) dexmedetomidine (10 µg kg-1; Dex); 3) maropitant (20 mg kg-1; Maro); 4) morphine (1.5 mg kg-1) + dexmedetomidine (5 µg kg-1; Mor + Dex); 5) dexmedetomidine (5 µg kg-1) + maropitant (10 mg kg-1; Dex + Maro); 6) morphine (1.5 mg kg-1) + maropitant (10 mg kg-1; Mor + Maro); 7) morphine (1 mg kg-1) + dexmedetomidine (3.5 µg kg-1) + maropitant (6.5 mg kg-1; Mor + Dex + Maro); and 8) normal saline (0.5 mL; saline), all injected intravenously. The tail-flick and hot-plate tests were performed before and 5, 15, 30, 45, 60, 90 and 120 minutes after the injection of the drugs. These variables were analysed with the effect-time area under the curve (AUC) analysis and a mixed linear model. RESULTS: Data were analysed in 94 rats. The rank order of the total analgesic effects of the treatment groups shown by AUC analysis was found to be Mor > Maro + Mor > Dex + Mor > Dex > Maro > Dex + Maro + Mor > Dex + Maro > saline for the hot-plate test, and Maro + Mor > Mor > Dex + Mor > Dex + Maro + Mor > Maro > Dex > Dex + Maro > saline for the tail-flick test. The mixed model analysis showed a significant difference between latencies of the group morphine + maropitant versus all other treatment groups in the tail-flick test (p < 0.0001) and morphine versus saline in the hot-plate test (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Morphine and maropitant appeared to show a supra-additive effect for analgesia in the tail-flick test. Clinical trials should be conducted to establish its use in treating pain.

Common occurrence of a unique Cryptosporidium ryanae variant in zebu cattle and water buffaloes in the buffer zone of the Chitwan National Park, Nepal.

There are very few studies on the diversity and public health significance of Cryptosporidium species in zebu cattle and water buffaloes in developing countries. In this study, PCR-restriction fragment length polymorphism and DNA sequence analyses of the small-subunit (SSU) rRNA gene were used to genotype Cryptosporidium specimens from 12 zebu cattle calves, 16 water buffalo calves, and four swamp deer (Cervus duvaucelii) collected from the buffer zone of the Chitwan National Park, Nepal. All Cryptosporidium specimens from cattle and buffaloes belonged to Cryptosporidium ryanae, whereas those from deer belonged to Cryptosporidium ubiquitum. Comparison of the SSU rRNA gene sequences obtained with those from earlier studies has identified a nucleotide substitution unique to all C. ryanae isolates from Nepal, in addition to some sequence heterogeneity among different copies of the gene. The finding of the dominance of a unique C. ryanae variant in both zebu cattle and water buffaloes in Nepal indicates that there is unique cryptosporidiosis transmission in bovine animals in the study area, and cross-species transmission of some Cryptosporidium spp. can occur between related animal species sharing the same habitats.