Efeitos cardiovasculares da medetomidina e cetamina em Puma concolor e tempo de recuperação após aplicação de ioimbina ou atipamezole / [Cardiovascular effects of medetomidine and cetamine in Puma concolor and recovery time after application of ioimbin or atipamezole]

O objetivo deste estudo foi avaliar as alterações cardiorrespiratórias causadas pela medetomidina associada à cetamina, e o tempo de recuperação após aplicação intramuscular de atipamezole ou ioimbina em Puma concolor. Para isso, foi realizada a aplicação de medetomidina (100µg/kg) associada à cetamina (5mg/kg) em 11 onças-pardas, sendo os parâmetros cardiorrespiratórios registrados a cada 15 minutos, durante 90 minutos de avaliação. Em seguida, a anestesia foi revertida com aplicação intramuscular de ioimbina (0,4mg/kg; n=5) ou atipamezole (0,25mg/kg; n=6), sendo analisado o tempo até a recuperação. Dos parâmetros cardiorrespiratórios avaliados, houve diferença apenas na frequência respiratória (entre os momentos 60 e 90 minutos), estando esta, todavia, dentro do intervalo de referência para a espécie. Além disso, verificou-se tempo para decúbito esternal significativamente menor nos animais do grupo atipamezole (18±7 minutos), quando comparado ao grupo ioimbina (36±17 minutos), entretanto o tempo de recuperação completa foi estatisticamente igual entre os dois reversores analisados. Assim, a associação anestésica promoveu anestesia eficiente, segura e de rápida indução em onças-pardas, permitindo a imobilização dos animais durante os 90 minutos de avaliação, sem a ocorrência de complicações. Ao se comparar a reversão anestésica com atipamezole e ioimbina, observou-se equivalência dos fármacos no tempo de recuperação completa dos animais.(AU)

The aim of this study was to evaluate the cardiorespiratory changes caused by ketamine-associated medetomidine, and the recovery time after intramuscular application of atipamezole or yohimbine in Puma concolor. For this, the application of medetomidine (100µg/kg) associated with ketamine (5mg/kg) was performed in eleven brown ounces, and the cardiorespiratory parameters were recorded every 15 minutes during 90 minutes of evaluation. Afterwards, anesthesia was reversed with intramuscular application of yohimbine (0.4mg/kg; n=5) or atipamezole (0.25mg/kg; n=6), and time to recovery was analyzed. Of the cardiorespiratory parameters evaluated, there was a difference only in respiratory rate (between 60 and 90 minutes), however, within the reference range for the species. In addition, there was a significantly shorter time for sternal decubitus in the animals of the atipamezole group (18±7 minutes) when compared to the yohimbine group (36±17 minutes), however the complete recovery time was statistically equal between the two reversers analyzed. Thus, the anesthetic association promoted efficient, safe and fast induction anesthesia in puma, allowing the animals to be immobilized during the 90 minutes of evaluation without complications. Comparing anesthetic reversal with atipamezole and yohimbine, drug equivalence was observed in the complete recovery time of the animals.(AU)

Estimation of yohimbine base in complex mixtures by quantitative HPTLC application.

The indole alkaloid Yohimbine has been used for over two centuries in the treatment of erectly dysfunction. Several formulations containing yohimbine salts, yohimbe bark power or extract are marketed worldwide. Determination of the amount of yohimbine in such formulation is a challenging task due to their complex nature. Extraction followed by acid-base purification resulted in a relatively pure alkaloids containing fractions. The exact amounts of yohimbine free base in different formulations were determined by densitometric HPTLC validated methods using silica gel TLC plates. Standard curve for yohimbine was generated using yohimbine hydrochloride subjected to the same acid-base treatment as the used samples. All formulations found to contain yohimbine though some with less concentration than the labeled amount.

A comparative study of ICH validated novel spectrophotometric techniques for resolving completely overlapping spectra of quaternary mixtures.

A pharmaceutically marketed mixture of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine co-formulated as a promising therapy for erectile dysfunction. Simultaneous determination of the aforementioned pharmaceutical formulation without prior separation steps was applied using mean centering of ratio spectra and triple divisor spectrophotometric methods. Mean centering of ratio spectra method depended on using the mean centered ratio spectra in three successive steps which eliminated the derivative steps and so the signal to noise ratio was improved. The absorption spectra of the prepared solutions were measured in the wavelength range of 215-300 nm in the concentration ranges of 1-15, 3-15, 1-20, and 3-15 µg mL(-1) for Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. The amplitudes of the mean centered third ratio spectra were measured at 250 nm and 268 nm for Yohimbine and Alpha-tocopheryl acetate, respectively and at peak to peak 272-273 and 262-263 nm for Niacin and Caffeine, respectively. In triple divisor method each drug in the quaternary mixture was determined by dividing the spectrum of the quaternary mixture by a standard spectrum of a mixture containing equal concentrations of the other three drugs. First derivative of these ratio spectra was obtained where determination could be achieved without any interference from the other three drugs. Amplitudes of 1-15, 3-15, 1-15, and 3-15 µg mL(-1) were used for selective determination of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. Laboratory prepared mixtures were analyzed by the developed novel methods to investigate their selectivity also, Super Act® capsules were successfully analyzed to ensure absence of interference from additives. The developed methods were validated according to the ICH guidelines. The proposed methods were statistically compared with each other and with the reported methods; using student t-test, F-test, and one way ANOVA, where no significant difference was found with respect to accuracy and precision.

Application of modern drug metabolism structure determination tools and assays to the in vitro metabolism of imiloxan.

Imiloxan is an alpha2 adrenoceptor antagonist and was developed for depression in the 1980's. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecule's development was discontinued. The present study revisits the in vitro metabolism of imiloxan using modern analytical methods. Human and rat liver microsomes convert imiloxan into a variety of metabolites many of which are unstable and or reactive. Imiloxan also yields high protein covalent binding in microsomal assays. Imiloxan is a useful test molecule for defining the relationship between liver covalent binding and idiosyncratic toxicity.