Protective effect of dexmedetomidine against organ dysfunction in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats

Dexmedetomidine (DEX), a selective agonist of α2-adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO2) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-β, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α2-adrenergic receptors.

Isolation and identification of the chemical constituents from cortex of african traditional medicinal Pausinystaliamacroceras P / 中国药学杂志

OBJECTIVE: To study the chemical constituents from cortex of African traditional medicine Pausinystalia macroceras P. METHQDS: Various column chromatographic techniques were used to isolate and purify the chemical constituents and their structures were elucidated by spectral analysis and chemical analysis. RESULTS: Nine compounds were isolated and identified as corynan-theidine(I), corynantheine(II), ajmalicine(III), yohimbine(IV), corynanthine(V), α-yohimbine(VI), α-yohimbine(VII), β-sitosterol(VI), ursolic acid(IX) and oleanolic acid(X). CONCLUSION: The compounds I, IV, VIII, IX and X are isolated from Pausinystalia macroceras P. for the first time.

Study of α1 adrenoceptor-mediated vasoconstriction and protein expressions induced by mmLDL in mouse mesenteric artery / 中国药理学通报

Aim To investigate the effects of mmLDL on the up-regulation ofα1 receptors in moues mesenter- ic arteries. Methods Mice tail intravenous injection of mmLDL was used . Vitro sensitive myograph was empl- oyed to examine Noradrenaline ( NA) induced vascular contraction on mice mesenteric artery, and the mRNA and protein expressions ofα1 andα2 receptors were an-alyzed by real-time PCR and Western blot, respective-ly. Results mmLDL significantly increased NA in-duced concentration-contractile curve, and the data of Emax and pEC50 were from ( 122. 61 ± 9. 40 )% and (5. 65 ± 0. 05 ) in normal saline ( NS ) group to (161. 01 ± 6. 90 )% and ( 6. 20 ± 0. 08 ) in mmLDL group (P tion-contractile curve induced by NA towards right. Af-ter using mmLDL, the mRNA and protein levels of α1 adrenoceptor were significantly increased, but the mR-NA and protein levels of α2 adrenoceptor were not changed. Conclusion Tail intravenous injection of mmLDL enhances the vascular expressions of α1 adre-noceptors and the contractile effects mediated byα1 ad-renoceptors.

Effect of agmatine co-administration with yohimbine on morphine-induced behavioral sensitization in mice / 国际药学研究杂志

Objective To investigate the effect of agmatine or agmatine combined with yohimbine on morphine-induced psychological dependence in mice. Methods 1. Testing the effect of agmatine or agmatin combined with yohimbine on basal locomotor activity in 60 minutes. C57BL/6J male mice were divided into four groups: control group, agmatine (1,10,20,40 and 80 mg/kg) groups, yohimbine (0.3,1,2 and 8 mg/kg) groups and yohimbine (2 mg/kg) + agmatine (80 mg/kg) group. 2. Testing theeffects of drug pretreatment on morphine-induced hyperlocomotion in 60 minutes. Mice were divided into five groups: control group, morphine (10 mg/kg) group, agmatine (1,20 and 80 mg/kg) + morphine (10 mg/kg) group,yohimbine (2 mg/kg) + morphine (10 mg/kg) group and yohimbine (2 mg/kg) + agmatine (80 mg/kg) + morphine (10 mg/kg) group. 3. Observing the effects of agmatine or agmatine combined with yohimbine on morphine induced behavioral sensitization. The mice were administrated with morphine (10 mg/kg) on the 1st , 4th and 7th day and the locomotor activity of mice was recorded for 60 minutes. Mice were divided into four groups: control group, morphine (10 mg/kg) group, agmatine (1,20 and 80 mg/kg) + morphine (10 mg/kg) groups and yohimbine (2 mg/kg) + agmatine (80 mg/kg) + morphine (10 mg/kg) group. Results Our present study showed that agmatine (1-80 mg/kg) or yohimbine (0.3-2 mg/kg), a selective antagonist of a2-adrenoceptor, had no significant effect on basal locomotor and acute morphine-induced hyperlocomotion compared with those of control group. However, the distance in the group of agmatine combined with yohimbine followed by morphine for 60 min was (22 581.6&11 694.0) cm, which was significantly lower than the acute morphine group(37 577.9±9 657.4) cm(#<0.05). In the mophine-induced behavioral sensitization model, agmatine (1,20 and 80 mg/kg) alone had no effect on morphine-induced development of behavioral sensitization in mice. But, the combination of the two drugs significantly attenuated morphine-induced behavioral sensitization. The locomotor activities in the combination treatment groups were (21 112.7±5 586.7) cm, (37 672.7±10 518.8) cm and 47 681.0±15 845.3 cm, which were lower than those of morphine group (31 156.4&8 010.5) cm(#<0.01), (51 724.9&11 364.51) cm (P<0.05) and (63 572.2&12 151.2) cm (P<0.05) on the 1st , 4th and 7th day of experiment, respectively. Conclusion Our current results demonstrated that agmatine combined with yohimbine could decrease morphine-induced psychological dependence in mice. It may provide a new strategy for psychological dependence of morphine.

Effect of agmatine co-administration with yohimbine on morphine-induced behavioral sensitization in mice / 国际药学研究杂志

Objective To investigate the effect of agmatine or agmatine combined with yohimbine on morphine-induced psychological dependence in mice. Methods 1. Testing the effect of agmatine or agmatin combined with yohimbine on basal locomotor activity in 60 minutes. C57BL/6J male mice were divided into four groups:control group, agmatine (1,10,20,40 and 80 mg/kg) groups, yohimbine(0.3,1,2 and 8 mg/kg) groups and yohimbine(2 mg/kg)+ agmatine(80 mg/kg) group. 2. Testing the effects of drug pretreatment on morphine-induced hyperlocomotion in 60 minutes. Mice were divided into five groups: control group, morphine(10 mg/kg) group, agmatine(1,20 and 80 mg/kg)+ morphine(10 mg/kg) group,yohimbine(2 mg/kg)+ morphine(10 mg/kg) group and yohimbine(2 mg/kg)+ agmatine(80 mg/kg)+ morphine(10 mg/kg) group. 3. Observing the effects of agmatine or agmatine combined with yohimbine on morphine induced behavioral sensitization. The mice were administrated with morphine(10 mg/kg) on the 1st , 4th and 7th day and the locomotor activity of mice was recorded for 60 minutes. Mice were divided into four groups: control group, morphine(10 mg/kg) group, agmatine(1,20 and 80 mg/kg) + morphine(10 mg/kg) groups and yohimbine (2 mg/kg)+ agmatine(80 mg/kg)+ morphine(10 mg/kg) group. Results Our present study showed that agmatine(1-80 mg/kg) or yohimbine (0.3-2 mg/kg), a selective antagonist of α2-adrenoceptor, had no significant effect on basal locomotor and acute morphine-induced hyperlocomotion compared with those of control group. However, the distance in the group of agmatine combined with yohimbine followed by morphine for 60 min was(22 581.6±11 694.0) cm,which was significantly lower than the acute morphine group(37 577.9±9 657.4)cm(P<0.05). In the mophine-induced behavioral sensitization model, agmatine(1,20 and 80 mg/kg) alone had no effect on morphine-induced development of behavioral sensitization in mice. But, the combination of the two drugs significantly attenuated morphine-induced behavioral sensitization. The locomotor activities in the combination treatment groups were (21 112.7±5 586.7)cm,(37 672.7±10 518.8)cm and(47 681.0±15 845.3)cm, which were lower than those of morphine group (31 156.4±8 010.5) cm(P<0.01),(51 724.9±11 364.51)cm(P<0.05) and(63 572.2±12 151.2) cm(P<0.05) on the 1st , 4th and 7th day of experiment, respectively. Conclusion Our current results demonstrated that agmatine combined with yohimbine could decrease morphine-induced psychological dependence in mice. It may provide a new strategy for psychological dependence of morphine.

Evaluation of the noradrenergic pathway and alpha-2 and beta-receptors in the modulation of the analgesia induced by transcutaneous electric nerve stimulation of high and low frequencies / Evaluación de la vía noradrenérgica y de los receptores alfa-2 y beta en la modulación de analgesia inducida por la estimulación eléctrica nerviosa transcutánea con alta y baja frecuencia / Avaliação da via noradrenérgica e dos receptores alfa-2 e beta na modulação da analgesia induzida pela estimulação elétrica nervosa transcutânea de alta e de baixa frequência

Transcutaneous electric nerve stimulation is a noninvasive method used in clinical Physiotherapy to control acute or chronic pain. Different theories have been proposed to explain the mechanism of the analgesic action of transcutaneous electric nerve stimulation, as the participation of central and peripheral neurotransmitters. The aim of this study was to evaluate the involvement of noradrenergic pathway and of the receptors alfa-2 and beta in the modulation of analgesia produced by transcutaneous electric nerve stimulation of high and low frequency in Wistar rats after chronic treatment with propranolol or yohimbine intraperitoneally. Animals weighing 200 to 300 g were divided into 9 groups (n=8), which were obtained nociceptive thresholds through the Tail Flick before and after application of TENS for comparing the change of pain. The administration of yohimbine or propranolol at a dose of 3 mg/kg was effective in antagonizing the analgesia induced by high (150 Hz) and low (10 Hz) frequency transcutaneous electric nerve stimulation according to ANOVA test followed by Duncan post hoc test (p<0.05). Thus, it is suggested the involvement of alpha-2 and beta noradrenergic receptors in the modulation of transcutaneous electric nerve stimulation-induced analgesia.

La estimulación eléctrica nerviosa transcutánea es un método no invasivo utilizado en la clínica de Fisioterapia para controlar el dolor agudo y crónico. Diversas teorías son propuestas para explanar el mecanismo de acción analgésico de la estimulación eléctrica nerviosa transcutánea, como la participación de neurotransmisores centrales y periféricos. El objetivo del presente estudio fue evaluar la participación de la vía noradrenérgica y de los receptores alfa-2 y beta en la modulación de analgesia inducida por la estimulación eléctrica nerviosa transcutánea con alta y baja frecuencia en ratos del tipo Wistar, después del tratamiento crónico con yohimbina o propranolol por la vía intraperitoneal. Animales que pesaban 200 y 300 g fueron divididos en nueve grupos (n=8), por los cuales fueron obtenidos los umbrales nociceptivos por medio del Tail Flick, antes y después de la aplicación de la estimulación eléctrica nerviosa transcutánea con el intuito de comparar la alteración del cuadro álgico. La administración de yohimbina o propranolol en el dosis de 3 mg/kg fue eficaz en resultar en una antagonización de analgesia inducida por la estimulación eléctrica nerviosa transcutánea con alta (150 Hz) y baja (10 Hz) frecuencia, de acuerdo al test de ANOVA seguido del test post-hoc de Duncan (p>0,05). Por lo tanto, se sugiere el envolvimiento de los receptores noradrenergicos alfa-2 y beta en la modulación de analgesia inducida por la estimulación eléctrica nerviosa transcutánea.

Estimulação elétrica nervosa transcutânea é um método não invasivo utilizado na clínica de Fisioterapia para controlar dores aguda ou crônica. Diferentes teorias são propostas para explicar o mecanismo de ação analgésica da estimulação elétrica nervosa transcutânea, como a participação de neurotransmissores centrais e periféricos. O objetivo do presente estudo foi avaliar a participação da via noradrenérgica e dos receptores alfa-2 e beta na modulação da analgesia induzida pela estimulação elétrica nervosa transcutânea de alta e baixa frequência em ratos Wistar, após tratamento crônico com ioimbina ou propranolol por via intraperitoneal. Animais pesando entre 200 e 300 g foram divididos em 9 grupos (n=8), dos quais se obteve os limiares nociceptivos por meio do Tail Flick antes e após a aplicação da estimulação elétrica nervosa transcutânea para comparação de mudança do quadro álgico. A administração de ioimbina ou de propranolol na dose de 3 mg/kg foi efetiva em causar uma antagonização da analgesia induzida pela estimulação elétrica nervosa transcutânea de alta (150 Hz) e baixa frequência (10 Hz) segundo teste ANOVA seguido do teste post hoc Duncan (p<0,05). Dessa forma, sugere-se o envolvimento de receptores noradrenérgicos alfa-2 e beta na modulação da analgesia induzida pela estimulação elétrica nervosa transcutânea. .

Effects of berberine and yohimbine on splenocyte apoptosis in septic mice / 中国病理生理杂志

[ ABSTRACT] AIM:To observe the effects of berberine and yohimbine on splenocyte apoptosis in septic mice and underlying mechanisms.METHODS:The mice were subjected to cecal ligature and puncture ( CLP) .The drugs or vehi-cle were given intragastrically 2 h after the surgery according to the following 5 groups:sham, CLP, CLP+berberine, CLP+yohimbine, and CLP+berberine+yohimbine.The apoptosis of splenocytes stained by TUNEL was observed under laser scanning confocal microscope 20 h after CLP.The splenic lymphocytes were isolated and observed using flow cytometry. The activities of caspase-3, caspase-8 and caspase-9 in splenic lymphocytes were detected, and the expression of Fas, Bim, Bcl-2 and Bax in the splenocytes was also determined by Western blotting.RESULTS:The TUNEL staining showed that the apoptotic rate of the splenocytes in septic mice 20 h after CLP was significantly higher than that in sham and CLP+yohimbine groups (P<0.05).Compared with CLP group, the proportion of apoptotic cells was decreased in septic mice in CLP+berberine+yohimbine and CLP+yohimbine groups ( P<0.05) .Flow cytometry analysis demonstrated the similar results in the apoptosis of splenocytes and T lymphocytes.However, only yohimbine treatment reduced the apoptosis of B lymphocytes in the spleen of sepsis-challenged mice.Compared with CLP group, caspase-9 activity was significantly re-duced in CLP+berberine group (P<0.05), the activities of caspase-3, caspase-8 and caspase-9 were all statistically re-duced (P<0.05) in CLP+yohimbine group and CLP+yohimbine+berberine group.CLP significantly increased the ex-pression of cytosolic Fas, Bim and mitochondrial Bax in the splenocytes, and decreased Bcl-2 expression compared with sham group.Compared with CLP group, the expression of cytosolic Bim and mitochondrial Bax in CLP+berberine group were reduced (P<0.05).Fas expression decreased only in CLP+yohimbine group (P<0.05).Berberine combined with yohimbine reduced the expression of cytosolic Fas, Bim and mitochondrial Bax in the septic mouse splenocytes ( P <0.05).CONCLUSION:Yohimbine reduces sepsis-induced splenic lymphocyte apoptosis in mice by inhibiting Fas expres-sion and in turn blocking both extrinsic and intrinsic apoptosis pathways.Berberine reduces Bim expression and inhibits caspase-9 activation, but not caspase-3 activation and apoptosis in the septic mouse splenocytes.Berberine combined with yohimbine reduces splenocyte apoptosis in the septic mice by inhibiting both extrinsic and intrinsic apoptotic pathways.

Effects of yohimbine on norepinephrine release by locus coeruleus in stressed rats / 中华行为医学与脑科学杂志

Objective To study the cellular and molecular modulation mechanisms of norepinephrine (NE) release in hypothalamus induced by electrical stimulation in locus coeruleus (LC) in the rat model of depression-like behavior.Methods The depression-like behavior model was established by combining separation and chronic unpredictable stress stimulations.After the model establishment,behavior tests were used to verify the success of modeling.NE release in the hypothalamus induced by electrical stimulation in LC was studied in real time and NE signal was recorded with carbon fiber electrode.The peak value,the time to peak and half-life period of NE signal in both group rats were measured and analysed.Results The bodyweight,score of open-field test,percentage of sucrose preference of model group rats ((263.9± 16.4) g,(19.4±7.9),(44.3± 10.8) ％) were significantly lower than those((314.3±24.3) g,(53.3± 19.0),(60.6± 13.3) ％) of control group(P＜0.01).The peak value of NE signal in the hypothalamus induced by electrical stimulation in locus coeruleus in depression-like behavior model rats((176.9±50.4) pA)was less than that((361.6±88.6) pA)in control group(P＜0.01),and the time to peak of NE signal was also shortened in depression-like behavior model group rats (P＜0.05).Intraperitoneal injection of yohimbine (3 mg/kg) potentiated electrical stimulation induced NE release in depression-like behavior model rats but not in control group.Conclusion The chronic unpredictable stresses attenuate the secretion of NE in the hypothalamus induced by electrical stimulation in LC in rats.Yohimbine,a presynaptic α2 receptor antagonist,increased NE release in hypothalamus in depression-like behavior model rats.These findings suggest that the LC projects functionally to the hypothalamus and the projection may contribute to the pathogenesis of depression.

Differences between Physostigmine- and Yohimbine-induced States Are Visualized in Canonical Space Constructed from EEG during Natural Sleep-wake Cycle in Rats

Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.

Involvement of Selective Alpha-2 Adrenoreceptor in Sympathetically Maintained Pain

OBJECTIVE: Peripheral nerve injury often leads to neuropathic pain, which is characterized by burning pain, allodynia, and hyperalgesia. The role of the sympathetic nervous system in neuropathic pain is a complex and controversial issue. It is generally accepted that the alpha adrenoreceptor (AR) in sympathetic nerve system plays a significant role in the maintenance of pain. Among alpha adrenoreceptor, alpha-1 receptors play a major role in the sympathetic mediated pain. The primary goal of this study is to test the hypothesis that sympathetically maintained pain involves peripheral alpha-2 receptors in human. METHODS: The study was a randomized, prospective, double-blinded, crossover study involving twenty patients. The treatments were : Yohimbine (30 mg mixed in 500 mL normal saline), and Phentolamine (1 mg/kg in 500 mL normal saline) in 500 mL normal saline at 70 mL/hr initially then titrated. The patients underwent infusions on three different appointments, at least one month apart. Thus, all patients received all 2 treatments. Pain measurement was by visual analogue scale, neuropathic pain questionnaire, and McGill pain questionnaire. RESULTS: There were significant decreases in the visual analogue scale, neuropathic score, McGill pain score of yohimnine, and phentolamine. CONCLUSION: We conclude that alpha-2 adrenoreceptor, along with alpha-2 adrenoreceptor, may be play role in sympathetically maintained pain in human.

The role of norepinephrine in down-regulation of visceral sensitivity in rats deprived of rapid eye movement sleep / 中华内科杂志

Objective To investigate the role of norepinephrine in the down-regulated visceral sensitivity of rats deprived of rapid eye movement(REM)sleep.Methods Twenty-four male Sprague- Dawley rats were randomly divided into 3 groups:cage-yoked rats as control(YC),rats with REM sleep deprivation(SD)and rats with yohimbine administered intraperitoneally after REM sleep deprivation(YSD).Flower pot technique was employed to make sleep deprivation model.YSD group was given vohimbine intraperitoneally at the 48th hour after REM sleep deprivation.After both SD and YSD groups had completed these processes,rats of all the three groups were given colorectal distension(CRD)and electromyogram (EMG)was recorded at the same time.The number of discharges of EMG and the threshold of Dain perception of the rats were observed to evaluate the visceral sensitivity.The thalamus,rectum and distal colon were taken after CRD;MAO-mRNA and TH-mRNA in three tissues were detected with RT-PCR.Resuits On 48th hour,the number of discharges of EMG in 10 seconds responding to CRD in group SD was significantly less than that in group YC and the threshold of pain perception in group SD was higher than that in group YC(P＜0.05).The number of discharge of EMG in group YSD was significantly more than that in group SD(P＜0.05).The expression of MAO-mRNA in group SD was lower than that in group YC(P＜0.05)and the expression of TH-mRNA in group SD was higher than that in group YC(P＜ 0.05).Conclusions The visceral sensitivity in rats is down-regulated by REM sleep deprivation,which can increase synthesis of norepinephrine.Norepinephrine can modulate visceral sensitivity.

Determination of Yohimbine in Corynanthe Yohimbe K. Schum. by HPLC / 中国药房

OBJECTIVE:To establish a HPLC method for the determination of yohimbine in corynanthe yohimbe K.schum.METHODS:The analysis was performed on C18 column with column under room temperature.The mobile phase consisted of methanol-phosphoric acid buffer-triethylamine(30∶ 70∶ 0.5,pH5.0)with a flow rate of 1.0mL? min-1.The wavelength was set at 270nm.RESULTS:There was a good linear relationship when the sample size of yohimbine was over a range of 10～ 1 000? g? mL-1(r=0.999 8),with recovery at 96.5% and precision at 1.23%.CONCLUSION:This method was simple and reliable,and suitable for the determination of content of yohimbine.

Noradrenergic Modulation of Spontaneous Inhibitory Postsynaptic Currents in the Hypothalamic Paraventricular Nucleus

Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE (30-100microM) reversibly decreased sIPSC frequency to 41+/-7% of the baseline value (4.4+/-0.8 Hz, p<0.001). This effect was blocked by yohimbine (2-20microM), an alpha2-adrenoceptor antagonist and mimicked by clonidine (50 microM), an alpha2-adrenoceptor agonist. In contrast, NE increased sIPSC frequency to 248+/-32% of the control (3.06+/-0.37 Hz, p<0.001) in 31 of 54 type II neurons, but decreased the frequency to 41+/-7% of the control (5.5+/-1.3 Hz) in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 M omega, p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via alpha2-adrenoceptor, however, either increases in about 60% or decreases in 40% of type II neurons.

The Effect of alpha2 Adrenoceptors and Imidazoline Receptors on the Mechanical Allodynia in Rats with Nerve Ligation Injury / 대한마취과학회지

BACKGROUND: Clonidine, an alpha2 adrenoceptor agonist, has been known to have an antiallodynic effect in many animal and human studies. Clonidine, however, acts on imidazoline receptors as well as alpha2 adrenoceptors. Recently, the effect of clonidine on the symapthetic nervous system was reported to be mediated via the activation of the imidazoline receptor system but not the alpha2 adrenergic receptor system. Therefore, we conducted a behavioral test to investigate the effects of alpha2 adrenoceptors and imidazoline receptors on mechanical allodynia in rats with spinal nerve ligation (SNL) injury. METHODS: Male Sprague Dawley rats were prepared with tight ligation of the left lumbar 5th and 6th spinal nerves and chronic lumbar intrathecal catheter implantation for drug administration. Using a von Frey hair (VFH) test, we examined the effects of intrathecal (IT) brimonidine (0.03 - 3 microgram), clonidine (3 - 10 microgram), and rilmenidine (1 - 30 microgram) in SNL rats. Measurements of the baseline value VFH test was conducted at each dose to compare with the preoperative state. In addition, an antagonistic study with rauwolscine or yohimbine was performed to investigate the reversal of antiallodynic effects of each agonist. Allodynic thresholds for the withdrawal response of the left lesioned hindpaw to VFH stimuli were assessed and converted to %MPE. RESULTS: The antiallodynic effects of brimonidine, clonidine, and rilmenidine were produced in a dose dependent manner. The antiallodynic effects of IT brimonidine but not rilmenidine were significantly antagonized by alpha2 antgonists rauwolscine and yohimbine (P < 0.05). CONCLUSIONS: The results suggest that mechanical allodynia produced by a SNL injury is reduced by an imidazoline receptor agonist as well as alpha2 adrenergic receptor agonists and sympathetic activation is more likely mediated by spinal imidazoline receptors.

Effects of Norepinephrine on the Mechanoreceptors of the Urinary Bladder in the Cat / 대한마취과학회지

BACKGROUND: Recent findings suggest that a coupling between the somatic and sympathetic nervous system is critical not only for the development but also for the maintenance of pain behavioral changes. However, studies on the effect of sympathetic efferent system on sensory receptors in the visceral organ that is more dependent on the autonomic nervous system are lacking. This study examined whether norepinephrine (NE) had an influence on the mechanoreceptors in the feline urinary bladder. METHODS: Ten adult male cats were used and anesthetized with alpha-chloralose and artificially ventilated. A cannula with the pressure transducer was inserted through the urethra to apply mechanical stimuli and monitor the pressure of bladder. A tiny cannula inserted into the bilateral side branches of vesical arteries were used as a route for a NE (10A.M 9:40 01-10-08 bilaterally) injection. Nerve fiber recordings were obtained from the distal stump of the pelvic nerve. RESULTS: After the NE injection, the response of mechanoreceptors (n = 13) to the isotonic pressure stimulus (50 - 60 mmHg) decreased significantly (p < 0.05) in terms of sensitivity (i.e., ratio of nerve activity change to urinary bladder pressure change). The responses to pressure stimuli after an injection of an alpha1 adrenoceptor blocker (terazosin) reversed the effect of NE. The responses of mechanoreceptors to isotonic pressure stimulus were not affected significantly by NE with preinjection of an alpha2 adrenoceptor blocker (yohimbine). CONCLUSIONS: These results suggest that NE may have influence on the sensitivity of mechanoreceptors in the normal feline urinary bladder via an alpha1 adrenoceptor.

Effects of Clonidine and Yohimbine on Neuropathic Pain in a Rat Model

OBJECTIVE: In a rat model of peripheral neuropathy, to determine whether neuropathic pain is related to the alpha-2 adrenergic receptor. METHOD: The neuropathic pain was produced by unilateral transection of the superior caudal trunk between the S3 and S4 spinal nerves. These animals showed the behavioral signs of neuropathic pain in the tail. Two weeks after the neuropathic surgery, tail withdrawal responses to the mechanical stimuli with von Frey hair (2.0 g) were examined 1, 2 and 24 hrs following the administration of clonidine, alpha-2 receptor agonist. One week after the clonidine test, the same behavioral test was done after the administration of clonidine along with yohimbine, alpha-2 receptor antagonist. RESULTS: Clonidine significantly reduced the frequency of tail response and yohimbine reversed the clonidine-induced anti-allodynic effect. CONCLUSION: These results suggest that neuropathic pain is related to the sympathetic nervous system via alpha-2 adrenergic receptor.

Effects of almitrine-raubasine on learning-memory ability in chronic episodic hypoxia rat and possible biochemical mechanism involved / 中华神经科杂志

Objective To investigate the effects of almitrine-raubasine on learning-memory ability and brain choline acetyltransferase (ChAT) activity in chronic episodic hypoxia (EHYP) rat. Methods After establishing the rat model of EHYP, almitrine-raubasine (0.03 tablets/250 g body weight , Bid) was given to the EHYP rats. The learning-memory ability was evaluated by using passive avoidance test and the ChAT activity in three different brain regions (including cerebral cortex, hippocampus and striatum) was determined using radiochemical method. Results As compared with the controlled rats, the performance on passive avoidance test of EHYP rats was impaired significantly (P

Effects of almitrine and raubasine on rehabilitation of ischemic stroke patient / 中华神经科杂志

Objective To assess the efficacy of almitrine and raubasine (Duxil) on post stroke rehabilitation Methods A clinical trial was done with a randomized, double blind, placebo controlled method Patients with ischemic stroke were included as having 1 month after the acute onset and receiving randomized treatment of either Duxil or placebo 2 tablets daily for 3 months The patients were assessed by using Barthel Index (BI), neurological functional deficit scores (NFDS), and Hasagawa dementia scales (HDS) each month after giving treatment Results In this study, only 74 cases were observed Of them, 38 patients received Duxil and 36 patients received placebo The baseline characteristics were compared between both groups Duxil was significantly shown more effective than placebo by increasing BI at 1, 2 or 3 months and by reducing NFDS at 1 month after treatment, more Duxil treated patients' NFDS had improved as compared with placebo treated patients In comparing with the pre treatment condition, there appeared a strong tendency of improvement in HDS with Duxil, although this significance was not confirmed by the difference of scores between two groups More Duxil treated patients than placebo controlled patients were reported having adverse events, but the difference was not significant at the 5% level All these events were mild, of short duration and resolved without treatment Conclusion Duxil can accelerate the recovery of nervous function to some degrees after stroke

Effect of Clonidine on the Pharmacodynamics and Recovery of Bupivacaine Neural Blockade / 대한마취과학회지

No abstract available.

A study of alpha adrenergic receptors in human and rabbit corpus cavernosum tissue / 대한비뇨기과학회지

The relaxation of the corpus cavernosum smooth muscle, which is main process in penile erection, is controlled by nerves that release cholinergic and nonadrenergic-noncholinergic neurotransmitters as well as vascular endothelium derived relaxing factor(EDRF). But the adrenergically-induced tone maintains the penis in flaccid state. In order to define the physiological role of adrenergic neurotransmission in the local control of penile erection we studied the distribution of alpha adrenergic receptor subtypes and their pharmacological potency in human and rabbit corpus cavernosum tissue. In this study we used yohimbine as the alpha-2 antagonist, which is known to have beneficial therapeutic effect for organic impotence, to assess its neuropharmacological mechanism in the treatment of erectile dysfunction. The alpha-1 : alpha-2 receptor potency was approximately 7.4:1 and 2.2:1 in human and rabbit tissue respectively. These results indicate that the predominant alpha adrenergic receptor is alpha-1 type and alpha-2 receptor antagonist, yohimbine, can not play a main role on the local control of penile erection because of its low receptor potency especially in human corpus cavernosum tissue. It remains possible that yohimbine partially antagonizes the postsynaptic alpha-1 mediated effect or activation of central sympathetic pathway is necessary for the therapeutic effect of yohimbine in human.