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

Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells / 中南大学学报(医学版)

OBJECTIVE@#To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
@*METHODS@#H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
@*RESULTS@#Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
@*CONCLUSION@#Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.

Modulation of WIN55, 212-2 state-dependent memory by alpha2-adrenergic receptors of the dorsal hippocampus

An overlapping distribution of alpha2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and alpha2-adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of alpha2-adrenergic receptors of the dorsal hippocampus on WIN55.212-2 state-dependent learning. Adult male Wistar rats were bilaterally implanted with chronic cannulae in the CA1 regions of their dorsal hippocampi trained in a step-down type inhibitory avoidance task and tested 24 hr after training, to measure step-down latency. Post-training or pre-test intra-CA1 administration of the cannabinoid receptor agonist, WIN 55,212-2 [0.25 and 0.5microg/rat] induced amnesia. Amnesia produced by post-training WIN55,212-2 [0.5 microg/rat] was reversed by pre-test administration of WIN55,212-2, that was due to a state-dependent effect. Pre-test intra-CA1 microinjections of clonidine [0.25, 0.5 and 1 microg/rat] or yohimbine [0.5, 0.75, and 1 MQ/rat] did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine [0.5 and 1 micro9/rat] or clonidine [0.25, 0.5, and 1 microg/rat] with an ineffective dose of WIN 55,212-2 [0.25 microg/rat] reversed post-training WIN55,212-2 [0.5 microg/rat,intra-CA1] induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine [1 microg/rat] before administration of WIN55,212-2 [0.5 microg/rat, intra-CA1], however, dose-dependently inhibited WIN55.212-2 state-dependent memory. Modulation of a2-adrenergic receptors in the dorsal hippocampal CA1 regions can influence WIN55, 212-2 induced amnesia and WIN55,212-2 state-dependent learning of an inhibitory avoidance task by pre- or post-synaptic mechanism[s]

Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alpha 2A adrenergic receptor (AR) is a subtype of α2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the α2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of α2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats.</p><p><b>METHODS</b>A total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 µg), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of α2A AR on inflammatory cells in BALF.</p><p><b>RESULTS</b>When compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as α2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-α and IL-1β were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-α, IL-1β and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-α and IL-1β were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-α, IL-1β and IL-6 in the BALF and the lung histopathological scores (r = 0.703, r = 0.595, r = 0.487 and r = 0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to α2A AR on inflammatory cells were also associated with the levels of TNF-α, IL-1β and IL-6 as well as the lung histopathologial scores (r = 0.803, r = 0.978, r = 0.716 and r = 0.808, respectively, P < 0.001).</p><p><b>CONCLUSIONS</b>Yohimbine can inhibit TNF-α, IL-1β and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of α2A AR on inflammatory cells.</p>

Effects of doxazosin enantiomers on alpha-adrenoceptors of isolated rabbit blood vessels / 药学学报

Doxazosin, a high selective alpha1-adrenoceptor antagonist, is considered as the first-line therapy for the patients with benign prostatic hyperplasia (BPH) and also produce several side effects in cardiovascular system. In this study, we observed the isometric vasoconstrictive responses of the rabbit isolated arterial rings to electric field stimulation and noradrenaline ( NA ) to study the effects of R-doxazosin ( R-DOX ) and S-doxazosin ( S-DOX ) on the alpha1-adrenoceptor-regulated vasoconstrictive responses in the rabbit isolated ear artery, mesenteric artery and pulmonary artery, and the effects of higher concentration of S-DOX and R-DOX on presynaptic alpha2-adrenoceptor-regulated purinergic vasoconstriction in the rabbit isolated saphenous artery. We found that R-DOX and S-DOX competitively inhibited the vasoconstriction induced by NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery. The pA2 values of R-DOX and S-DOX against NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery were 7. 91 +/- 0. 03 and 7. 53 +/- 0. 05, 7. 80 +/- 0. 05 and 7. 29 +/-0. 07, 8. 32 +/- 0. 06 and 7. 97 +/- 0. 07, respectively. The pA2 values of R-DOX in the three arterial preparations were significantly higher than those of S-DOX (P < 0. 01). R-DOX and S-DOX at the concentrations of 0. 1 - 10 micromol x L (-1) did not affect the vasoconstriction induced by electric stimulation in the rabbit isolated saphenous artery. R-DOX and S-DOX at 100 micromol x L(-1) in the rabbit isolated saphenous artery completely inhibited the vascular responses to exogenous NA, but did not affect the vascular responses to exogenous adenosine triphosphate (1 mmol x L(-1) ). It is reasonable to suggest that R-DOX and S-DOX competitively inhibit the vasoconstriction induced by NA in the rabbit ear artery, mesenteric artery and pulmonary artery, and the pA2 values of S-DOX are significantly lower than those of R-DOX. The higher concentration (10 micromol x L(-1)) of R-DOX and S-DOX does not affect the presynaptic alpha2-adrenoceptors at sympathetic nerve terminals of the rabbit saphenous artery.