Manic psychosis associated with ginseng: a report of two cases and discussion of the literature.

BACKGROUND: Herbal medicine use, highly prevalent in the general population, is often a neglected component of the medical history. Herbs are presumed safe because they are "natural" self-care products. We call attention to the following issues: Panax ginseng, one of the most frequently used herbal medicines, has complex pharmacological activity, and can be associated with severe psychiatric symptoms. Physicians may be unfamiliar with herbal therapy risks, and the need for further education and systematic research is highlighted. OBJECTIVE: To describe two cases of new onset manic psychoses associated with high dose, chronic ginseng use, and review the relevant literature. CASE REPORTS: A 23-year-old man developed acute mania after one month of daily ginseng use and intermittent cannabis use. A 79-year-old man developed hypomania while using ginseng and yohimbine for erectile dysfunction, and had a recurrence of mania after stopping yohimbine but increasing his daily intake of ginseng. CONCLUSIONS/SUMMARY: Symptoms of mania fully remitted within days upon discontinuation of ginseng and supportive treatment. Available data prevent a clear determination of causation; however, ginseng-induced mania in the these and previous case reports is suggested by the following: patients had no prior psychiatric history, daily use of ginseng was temporally associated with mania onset, patients ingested much higher doses for a longer duration than recommended in Traditional Chinese Medicine (TCM), and withdrawal of ginseng led to rapid remission. Generally well tolerated, many physicians are unaware that ginseng may be associated with acute and significant psychiatric disturbances for certain at-risk individuals.

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. .

Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects.

BACKGROUND: Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist-possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. METHODS: Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6-8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. RESULTS: A condition effect was noted for both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p > 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. CONCLUSION: Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women.

[Intraventricular yohimbine infusion induces noradrenergic changes in motor cerebral injured rats and enhances motor recovery]. / La infusión de yohimbina induce cambios noradrenérgicos en ratas con daño cerebral motor y facilita la recuperación funcional motora.

INTRODUCTION: It has been proposed that noradrenaline is one of the neurotransmitters involved in the functional recovery. In this sense, it has been proposed that the alpha-2 noradrenergic receptors play an important role in the functional reinstatement. OBJECTIVE: the aim of this work was to study the role of the alpha-2 noradrenergic receptors on the noradrenaline contents in cerebellum and pons of rats iron-injured in the motor cortex. METHODS: Fifteen male Wistar rats were allocated in three groups: control (n = 5) with intracortical infusion of saline (0.9%), injured (n = 5) with intracortical infusion of dextran iron and intraventricular infusion of saline, and injured + yohimbine (alpha-2 receptor antagonist; n = 5) that received an intracortical infusion of dextran iron and also an intraventricular infusion of yohimbine. Motor behavior was assessed by means of the beam-walking paradigm. Three days after surgeries, the animals were sacrificed and the left and right sides of the pons and the cerebellar hemispheres were extracted. Tissues were prepared for noradrenaline analysis by means of high performance liquid chromatography. RESULTS: We observed that the yohimbine-treated animals had a noradrenaline increase in the right side of the pons and a decrease in the right cerebellar hemisphere. CONCLUSION: It is concluded that the blockage of the alpha-2 receptors leads to an increase of noradrenaline in the locus coeruleus, which retards the effects of the cerebral injury.

Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized, placebo controlled, cross-over study.

BACKGROUND: We have recently reported that the dietary supplement Meltdown increases plasma norepinephrine (NE), epinephrine (EPI), glycerol, free fatty acids (FFA), and metabolic rate in men. However, in that investigation measurements ceased at 90 minutes post ingestion, with values for blood borne variables peaking at this time. It was the purpose of the present investigation to extend the time course of measurement to 6 hours, and to include women within the design to determine if sex differences to treatment exist. METHODS: Ten men (24 +/- 4 yrs) and 10 women (22 +/- 2 yrs) ingested Meltdown or a placebo, using a randomized, cross-over design with one week separating conditions. Blood samples were collected immediately before supplementation and at one hour intervals through 6 hours post ingestion. A standard meal was provided after the hour 3 collection. Samples were assayed for EPI, NE, glycerol, and FFA. Five minute breath samples were collected at each time for measurement of metabolic rate and substrate utilization. Area under the curve (AUC) was calculated. Heart rate and blood pressure were recorded at all times. Data were also analyzed using a 2 (sex) x 2 (condition) x 7 (time) repeated measures analysis of variance, with Tukey post hoc testing. RESULTS: No sex x condition interactions were noted for AUC for any variable (p > 0.05). Hence, AUC data are collapsed across men and women. AUC was greater for Meltdown compared to placebo for EPI (367 +/- 58 pg x mL(-1) x 6 hr(-1) vs. 183 +/- 27 pg x mL(-1) x 6 hr(-1); p = 0.01), NE (2345 +/- 205 pg x mL(-1) x 6 hr(-1) vs. 1659 +/- 184 pg x mL(-1) x 6 hr(-1); p = 0.02), glycerol (79 +/- 8 microg x mL)-1) x 6 hr(-1) vs. 59 +/- 6 microg x mL(-1) x 6 hr(-1); p = 0.03), FFA (2.46 +/- 0.64 mmol x L(-1) x 6 hr(-1) vs. 1.57 +/- 0.42 mmol x L(-1) x 6 hr(-1); p = 0.05), and kilocalorie expenditure (439 +/- 26 kcal x 6 hrs(-1) vs. 380 +/- 14 kcal x 6 hrs(-1); p = 0.02). No effect was noted for substrate utilization (p = 0.39). Both systolic and diastolic blood pressure (p < 0.0001; 1-16 mmHg), as well as heart rate (p = 0.01; 1-9 bpm) were higher for Meltdown. No sex x condition x time interactions were noted for any variable (p > 0.05). CONCLUSION: Ingestion of Meltdown results in an increase in catecholamine secretion, lipolysis, and metabolic rate in young men and women, with a similar response for both sexes. Meltdown may prove to be an effective intervention strategy for fat loss, assuming individuals are normotensive and their treatment is monitored by a qualified health care professional.

Antagonistic effects of yohimbine in pigs anaesthetised with tiletamine/zolazepam and xylazine.

Twelve healthy two-month-old Landrace x Yorkshire pigs of both sexes were randomly assigned to receive either tiletamine and xylazine (zx) or zolazepam and xylazine followed 20 minutes later by yohimbine (zxy). The pigs' scores for immobilisation and analgesia, and their rectal temperature, heart rate, respiration rate, pO(2), pCO(2), alkaline phosphatase, aspartate aminotransferase, glucose and total plasma proteins were determined before and five, 25, 45, 65 and 85 minutes after the administration of the tiletamine/zolazepam and xylazine. The mean total scores for immobilisation and analgesia of the zxy pigs were significantly lower than those of the zx pigs after 85 minutes. The mean rectal temperatures of the zxy pigs were significantly lower than those of zx pigs after 25, 45 and 65 minutes. The mean respiratory rates of the zx pigs were significantly lower than those of zxy pigs after five minutes. The mean pCO(2) of the zxy pigs were significantly lower than those of zx pigs five minutes after the administration of yohimbine. The mean glucose concentration of the zxy pigs were significantly lower than those of zx pigs after 65 and 85 minutes. The mean concentration total protein of the zxy pigs were significantly lower than those of zx pigs throughout the period of anaesthesia. Both groups became laterally recumbent within three minutes. When recovering from anaesthesia, the pigs treated with yohimbine took significantly less time to achieve sternal recumbency (mean [sd] 52.2 [8.9] v 76.2 [20.6] minutes) and less time to be able to stand (mean [sd] 77.0 [9.8] v 98.7 [15.8] minutes), and walk (mean [sd] 81.3 [11.3] v 110.8 [18.6] minutes).

Role of alpha2 receptors in quercetin-induced behavioral despair in mice.

Depression is a well-defined illness that afflicts a large population worldwide. Various biochemical theories have been described; however, the pathophysiology of depression is still poorly understood. The present study explores the role of a natural flavonoid, quercetin, in the forced swimming model of depression and its interaction with presynaptic alpha(2) adrenoceptors. Quercetin induced a significant behavioral despair, which was abrogated with pretreatment with yohimbine, an alpha(2) adrenoceptor antagonist, and imipramine, a tricyclic antidepressant. The results of the study support the contention that quercetin utilizes presynaptic alpha(2) adrenoceptors in eliciting its depressant activity in mice.

Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine.

The alpha2 adrenoceptor antagonist yohimbine (YO) increases transmitter release from adrenergic/noradrenergic (NA) neurons. Systemic YO activates the hypothalamic-pituitary-adrenal (HPA) axis, inhibits feeding, and supports conditioned flavor avoidance (CFA) in rats. To determine whether these effects require NA inputs to the bed nucleus of the stria terminalis (BNST), vehicle or saporin toxin conjugated to an antibody against dopamine beta hydroxylase (DSAP) was microinjected bilaterally into the BNST to remove its NA inputs. Subsequent tests failed to reveal any lesion effect on the ability of YO (5.0 mg/kg, i.p.) to inhibit food intake or to support CFA. Conversely, HPA axis responses to YO were significantly blunted in DSAP rats. In a terminal experiment, DSAP and control rats were perfused 90-120 min after intraperitoneal injection of YO or vehicle. Brains were processed to reveal Fos immunolabeling and lesion extent. NA fibers were markedly depleted in the BNST and medial parvocellular paraventricular hypothalamus (PVNmp) in DSAP rats, evidence for collateralized NA inputs to these regions. DSAP rats displayed significant loss of caudal medullary NA neurons, and markedly blunted Fos activation in the BNST and in corticotropin-releasing hormone-positive PVNmp neurons after YO. We conclude that a population of medullary NA neurons provides collateral inputs to the BNST and PVNmp, and that these inputs contribute importantly to Fos expression and HPA axis activation after YO treatment. Conversely, NA-mediated activation of BNST and PVNmp neurons is unnecessary for YO to inhibit food intake or support CFA, evidence for the sufficiency of other intact neural pathways in mediating those effects.

Role of hypothalamic alpha-adrenoceptor activity in fructose-induced hypertension.

The aim of the present study was to investigate the effects of the alpha2-adrenoceptor antagonist yohimbine on blood pressure and heart rate (HR) regulation, as well as on adrenergic and serotoninergic neurotransmission, in fructose hypertensive (F) rats. The anterior hypothalamic area of control (C) and F rats was perfused with Ringer's solution containing 10 and 100 microg/mL yohimbine through a microdialysis concentric probe. The effects of yohimbine on mean arterial pressure (MAP) and HR, as well as on hypothalamic dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) levels, were measured according to perfusion time. Although intrahypothalamic perfusion of yohimbine increased blood pressure in C rats (DeltaMAP 9 +/- 1 and 11 +/- 2 mmHg for 10 and 100 microg/mL yohimbine, respectively; P < 0.05 vs Ringer's perfusion), the alpha-adrenoceptor antagonist did not modify MAP in F. Intrahypothalamic yohimbine had no effect on HR at either concentration tested. Intrahypothalamic perfusion of 10 and 100 microg/mL yohimbine increased DOPAC levels in C rats (135 +/- 6 and 130 +/- 5% of basal levels, respectively; both n = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 +/- 6 and 102 +/- 6% of basal levels, respectively; both n = 6). In both C and F rats, yohimbine administration induced an increase in 5-HIAA dialysate levels. The results of the present study support the notion that alpha2-adrenoceptor tone of the anterior hypothalamus of normotensive rats, which contributes to normal blood pressure regulation, is not involved in the control of HR in either normotensive C or hypertensive F rats. The absence of changes in MAP after yohimbine perfusion in F rats suggests that the alpha2-adrenoceptor tone could be decreased in this group of rats and that this may be responsible for the maintenance of hypertension in this model. Intrahypothalamic perfusion of yohimbine increased DOPAC in the dialysate only in C rats, suggesting changes in presynaptic alpha2-adrenoceptor activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not differ between C and F groups.

Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: Mediation by alpha2-Adrenoceptors.

The antinociceptive effect and the mechanism of bee venom acupuncture (BVA) on inflammatory pain, especially in the rat model of collagen-induced arthritis (CIA), have not yet been fully studied. This study was designed to investigate the antinociceptive effect and its mu-opioid and alpha2-adrenergic mechanism of BVA in the CIA rat model. To induce CIA, male Sprague-Dawley rats were immunized with bovine type II collagen emulsified in Freund's incomplete adjuvant followed by a booster injection 14 days later. The antinociceptive effect was evaluated by tail flick latency (TFL). After induction of arthritis, the inflammatory pain threshold decreased as time passed, and there was no big change of the pain threshold after 3 weeks. Three weeks after the first immunization, BVA (0.25 mg/kg) injected into the Zusanli acupoint (ST36) showed the antinociceptive effect. Furthermore, the antinociceptive effect of BVA was blocked by yohimbine (alpha2-adrenergic receptor antagonist, 2 mg/kg, i.p) pretreatment, but not by naloxone (mu-opioid receptor antagonist, 2 mg/kg, i.p.) pretreatment. These results suggest that BVA can relieve inflammatory pain in CIA and the antinociceptive effect of BVA can be mediated by alpha2-adrenergic receptor.

Efeitos hemogasométricos da xilazina e da romifidina em cabras tratadas por ioimbina / Haemogasometric effects of xylazine and romifidine in goats treated with yohimbine

Estudaram-se as alterações produzidas por doses equipotentes de xilazina e romifidina e os efeitos da administração subseqüente de ioimbina em oito cabras mestiças. Respeitou-se um intervalo de sete dias entre os seguintes tratamentos: A- 250µg/kg/IM de xilazina e 0,1ml/kg/IV de solução fisiológica, B- 250µg/kg/IM de xilazina e 250µg/kg/IV de ioimbina, C- 25µg/kg/IM de romifidina e 0,1ml/kg/IV de solução fisiológica, D- 25µg/kg/IM de romifidina e 250µg/kg/IV de ioimbina. Foram mensurados a freqüência respiratória, o pH, as pressões parciais de oxigênio e dióxido de carbono, a concentração de íon bicarbonato, o excesso de bases e a saturação de oxigênio no sangue arterial. Utilizou-se um delineamento experimental crossover, e as médias foram comparadas pelo teste Duncan (Pmenor ou igual a 0,05). Xilazina e romifidina reduziram a pressão arterial de oxigênio e aumentaram a pressão arterial de dióxido de carbono. A ioimbina reverteu os efeitos da xilazina e da romifidina sobre as pressões parciais de oxigênio e dióxido de carbono no sangue arterial.

Complementary therapies for reducing body weight: a systematic review.

The prevalence of obesity is increasing at an alarming rate and a plethora of complementary therapies are on offer claiming effectiveness for reducing body weight. The aim of this systematic review is to critically assess the evidence from randomized controlled trials (RCTs) and systematic reviews of complementary therapies for reducing body weight. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until January 2004. Hand-searches of relevant medical journals and bibliographies of identified articles were conducted. There were no restrictions regarding the language of publication. Trial selection, quality assessment and data abstraction were performed systematically and independently by two authors. Data from RCTs and systematic reviews, which based their findings on the results of RCTs, were included. Six systematic reviews and 25 additional RCTs met our inclusion criteria and were reviewed. The evidence related to acupuncture, acupressure, dietary supplements, homeopathy and hypnotherapy. Except for hypnotherapy, Ephedra sinica and other ephedrine-containing dietary supplements the weight of the evidence is not convincing enough to suggest effectiveness. For these interventions, small effects compared with placebo were identified. In conclusion, our findings suggest that for most complementary therapies, the weight of the evidence for reducing body is not convincing. Hypnotherapy, E. sinica and other ephedrine-containing dietary supplements may lead to small reductions in body weight. However, the intake of E. sinica and ephedrine is associated with an increased risk of adverse events. Interventions suggesting positive effects in single RCTs require independent replication.

Spinal 5-HT(2) and 5-HT(3) receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats.

Transcutaneous electrical nerve stimulation (TENS) is a form of non-pharmacological treatment for pain. Involvement of descending inhibitory systems is implicated in TENS-induced analgesia. In the present study, the roles of spinal 5-HT and alpha(2)-adrenoceptors in TENS analgesia were investigated in rats. Hyperalgesia was induced by inflaming the knee joint with 3% kaolin-carrageenan mixture and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The (1). alpha(2)-adrenergic antagonist yohimbine (30 microg), (2). 5-HT antagonist methysergide (5-HT(1). and 5-HT(2). 30 microg), one of the 5-HT receptor subtype antagonists, (3). NAN-190 (5-HT(1A), 15 microg), (4). ketanserin (5-HT(2A), 30 microg), (5). MDL-72222 (5-HT(3), 12 microg), or (6). vehicle was administered intrathecally prior to TENS treatment. Low (4 Hz) or high (100 Hz) frequency TENS at sensory intensity was then applied to the inflamed knee for 20 min and PWL was determined. Selectivity of the antagonists used was confirmed using respective agonists administered intrathecally. Yohimbine had no effect on the antihyperalgesia produced by low or high frequency TENS. Methysergide and MDL-72222 prevented the antihyperalgesia produced by low, but not high, frequency TENS. Ketanserin attenuated the antihyperalgesic effects of low frequency TENS whereas NAN-190 had no effect. The results from the present study show that spinal 5-HT receptors mediate low, but not high, frequency TENS-induced antihyperalgesia through activation of 5-HT(2A) and 5-HT(3) receptors in rats. Furthermore, spinal noradrenergic receptors are not involved in either low or high frequency TENS antihyperalgesia.

Gastrointestinal transit in mice treated with various extracts of date (Phoenix dactylifera L.).

Dates are commonly consumed, especially in the Middle East, but their effect on gastrointestinal transit (GIT) has not been quantified. The effect of water and ethanol extracts from date flesh and date pits on the GIT in mice was studied. Fasted unanaesthetized male mice received by gavage either the vehicle (0.02 m/kg), or the extracts at doses of 0.01, 0.02 or 0.04 ml/kg. Two separate groups received either clonidine (1 mg/kg) or yohimbine (2 mg/kg). Two hours later, all animals were given a test meal containing charcoal and gum arabic in water. Thirty min thereafter, they were killed and the distance the charcoal column had traveled along the small intestine was measured. Compared with the control, the animals that received the ethanol and water extracts of both date flesh and pits emptied, in a dose-dependent manner, more of their gastrointestinal content. The increase in the GIT ranged from 4 to 22%. However, water extract from dialyzed date flesh induced a dose-dependent decrease in GIT that ranged from 4 to 24%. Clonidine exerted a significant decrease (68%), and yohimbine a significant increase (30%) in the GIT. Depending on the method of extraction, the date extracts may exert an increase or a decrease in GIT.

[Effective "home remedies" in orthostatic hypotension. A glass of water before getting up and a brick under the bed]. / Wirksame "Hausmittel" gegen die orthostatische Hypotonie. Ein Glas Wasser vor dem Aufstehen und ein Ziegelstein unterm Bett.

The symptoms of orthostatic hypotension can be considerably improved by non-pharmacological treatment, and patients with such symptoms should not initially be given medication. Many patients, for example, show a pronounced increase in blood pressure shortly after drinking water, and this phenomenon can be utilized to ameliorate symptoms. In patients who respond inadequately, treatment with pharmacological agents is indicated. The most appropriate drug needs to be selected individually on the basis of its action and tolerability. All medications suitable for treating orthostatic hypotension can appreciably increase the blood pressure in the prone patient.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Locus coeruleus modulates thalamic nociceptive responses via adrenoceptors.

This study investigated the parafascicular (PF) neuronal nociceptive responses and their modulation following electrical stimulation of the locus coeruleus (LC) and intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of two alpha-adrenoceptor antagonists, the alpha2-antagonist, yohimbine, and the alpha1-antagonist, prazosin. The main results were as follows: (1) the nociceptive evoked discharges in PF neurons were suppressed by preceding stimulation of LC; (2) the suppressive effect of LC stimulation on PF neurons was replaced by a facilitatory effect following pretreatment of i.t. yohimbine in 14 units tested, while i.t. prazosin failed to alter the LC-induced suppression, even when the prazosin dose was doubled; (3) i.c.v. pretreatment with prazosin strengthened the suppressive effect of LC stimulation on PF neurons; (4) i.c.v. norepinephrine (NE) administration induced, in PF neurons, a biphasic response to noxious stimulation; an early, brief (about 10 min) inhibitory effect followed by a late, long-lasting facilitatory effect; and (5) i.c.v. pretreatment of yohimbine or prazosin prevented the inhibitory or facilitatory responses released by NE, respectively. These results provide evidence that: (1) the LC-descending projections exhibit a suppressive effect on nociceptive transmission at the spinal level through alpha2-receptors; and (2) the LC-ascending projections exhibit dual effects, facilitatory and inhibitory, at the medial thalamus (PF) level through alpha1- and alpha2-receptors, respectively.

Effect of Japanese angelica root extract on pentobarbital-induced sleep in group-housed and socially isolated mice: evidence for the central action.

We investigated the effect of the aqueous extract of Japanese angelica root (JAR) on pentobarbital (PB) sleep in group-housed and socially isolated mice. The JAR extract (1.25-2.5 g/kg, p.o.) dose-dependently reversed the decrease in PB sleep caused by isolation stress without affecting PB sleep in group-housed mice. The JAR extract (2.5 g/kg, p.o.) also antagonized the decrease in PB sleep caused by the alpha 2-adrenoceptor antagonists yohimbine and idazoxan (1 mg/kg, i.p.) and the alpha 1-adrenoceptor agonist methoxamine (200 nmol, i.c.v.) in group-housed mice. These results suggest that the JAR extract reverses changes in the arousal level caused by isolation stress and the activation of central noradrenergic systems.

Amygdaloid noradrenaline is involved in the sensitization of the acoustic startle response in rats.

The present study examined the role of noradrenaline (NA) in the central nucleus of the amygdala (cA) in the sensitization of the acoustic startle response (ASR) in rats. In the first experiment, local microinjections of 0, 0.5, 1, 2 nmol of the alpha 2-adrenergic antagonist yohimbine into the cA increased the magnitude of the ASR in a dose-dependent way. In the second experiment, foot shocks were applied to increase the ASR amplitude (sensitization). Local microinjections of 0, 4, 8, 16 nmol of the alpha 2-adrenergic agonist ST-91 into the cA dose dependently decreased the sensitizing effects of foot shocks on the amplitude of the ASR. It is conjectured that yohimbine increases and ST-91 decreases local NA release by acting at presynaptic autoreceptors. The present data suggest that the release of NA in the cA is involved in the mediation of the sensitizing effects of foot shocks on the ASR.

Effects of yohimbine as a reversing agent for ketamine-xylazine anesthesia in budgerigars.

Fourteen adult budgerigars (Melopsittacus undulatus) were anesthetized with a combination of ketamine hydrochloride (40 mg/kg) and xylazine hydrochloride (10 mg/kg) intramuscularly. Forty-five minutes after ketamine-xylazine injection, one of four yohimbine hydrochloride doses (0.0, 0.11, 0.275, or 0.44 mg/kg, IM) was administered in a 0.7% saline vehicle. Latencies were recorded in minutes from yohimbine injection until subjects' behavior indicated three different points of recovery: 1) lifting the head, 2) standing unaided without ataxia, and 3) perching. Means for all three recovery point latencies were significantly reduced by 0.275 mg/kg of yohimbine compared with saline vehicle alone. Mean latencies among treatment groups for each of the three recovery points were not significantly different, other than control versus treated groups. Based on these results, we recommend a yohimbine dose of 0.275 mg/kg as an effective reversing agent for ketamine-xylazine anesthesia in budgerigars.