Acupuncture for the Treatment of Depression and Physical Symptoms in Chronic Bipolar Disorder: A Case Report.

INTRODUCTION: Bipolar disorder (BD) is typically treated by pharmacotherapy. However, pharmacotherapy alone is often not adequate to cope with the variety of symptoms associated with BD. The present case report describes the therapeutic effects of manual acupuncture on a patient with chronic BD, and multiple concurrent physical symptoms, that did not improve with standard pharmacotherapy. CASE: A 41-year-old woman with type II BD presented with depression, anxiety, and multiple physical symptoms. Her symptoms had first appeared 12 years prior, and she was diagnosed with type II BD 3 years after symptom onset. Although she received standard treatment, including medication and psychotherapy, her symptoms did not improve. Acupuncture treatment aimed at improving psychiatric and physical symptoms was performed weekly for 12 weeks. Depression and anxiety symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS) respectively. A visual analog scale (VAS) was used to evaluate physical symptoms including diarrhea, insomnia, and general malaise. Outcome measures were evaluated before each treatment. RESULTS: Throughout the course of the acupuncture intervention, no changes were made to the patient's psychotropic medication regimen. HSDS and HSAS scores decreased after 12 weeks of acupuncture treatment and improvements in all physical symptoms, as measured by the VAS, were observed. Furthermore, psychiatric symptoms with hypomanic or mixed features were not exacerbated. CONCLUSIONS: In this patient, acupuncture was effective in improving psychiatric and physical symptoms of type II BD. This non-pharmacological intervention may be a viable option for the treatment of BD-associated symptoms.

Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952.

Optimization of novel azetidine compounds, which we had found as colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors, provided JTE-952 as a clinical candidate with high cellular activity (IC50 = 20 nM) and good pharmacokinetics profile. JTE-952 was also effective against a mouse collagen-induced model of arthritis (mouse CIA-model). Additionally, the X-ray co-crystal structure of JTE-952 with CSF-1R protein was shown to be a Type II inhibitor, and the kinase panel assay indicated that JTE-952 had high kinase selectivity.

Discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by the use of docking models.

We report the discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by using a structure-based drug design (SBDD) based on a docking model. The work leads to the representative compound 4a with high CSF-1R inhibitory activity (IC50 = 9.1 nM). The obtained crystal structure of an azetidine compound with CSF-1R, which matched our predicted docking model, demonstrates that the azetidine compounds bind to the DFG-out conformation of the protein as a Type II inhibitor.

Dexmedetomidine dose-dependently enhances local anesthetic action of lidocaine.

PURPOSE: The combination of α2-adrenoceptor agonists, such as dexmedetomidine (DEX) and clonidine, with local anesthetics has been found to extend the duration of peripheral nerve blocks, probably owing to the resultant local vasoconstriction in the peripheral nerves. However, because the clear elucidation of the effect of DEX requires examination of the local anesthetic effect with DEX alone and the combination of various concentrations of DEX with local anesthetics, we evaluated the local anesthetic effect of various concentrations of DEX alone and with a local anesthetic. MATERIALS AND METHODS: The present study assessed the tail-flick (TF) latencies after injection of the appropriate drug in male Sprague-Dawley rats, using an epidural model that allowed constant pain stimulation intensity, dispersion of the anesthetic, and a precise injection site and dose. Lidocaine alone, lidocaine with 2.5-ppm DEX, lidocaine with 5.0-ppm DEX, lidocaine with 7.5-ppm DEX, and DEX alone were administered at the predetermined dose. The TF latency changes over time were compared using repeated measures analysis of variance (ANOVA). Comparisons among the groups were analyzed using ANOVA followed by a post hoc Dunnett's multiple comparison test or Tukey's multiple comparison test. RESULTS: The addition of DEX to lidocaine increased the TF latency and dose-dependently prolonged its duration as follows: 0-ppm DEX, 20 minutes; 2.5-ppm, 40 minutes; 5.0-ppm, 40 minutes; and 7.5-ppm, 50 minutes. DEX alone did not change the TF latency. CONCLUSIONS: Our results have demonstrated that DEX dose-dependently enhances the local anesthetic action of lidocaine in a rat TF model.

Establishment of an animal model of sedation using epidural anesthesia that uses the tail-flick test for evaluating local anesthetic effects in rats.

The tail-flick (TF) test is the most frequently used method to measure pain levels and assess the effects of anesthesia. In this study, we performed the TF test in rats sedated via an indwelling epidural catheter and then examined the effectiveness of this method in evaluating the local anesthetic effects. First, an epidural catheter was inserted into the epidural space, and anesthetic [lidocaine (L) or lidocaine including adrenaline (AL)] or normal saline (NS) was administered. Under sedation, we measured the dose for disappearance of the TF response, time to TF response recovery, onset and regression of local anesthesia, as well as the effect of an added agent on its continuation. The time course of TF latency (% maximum possible effect) in the NS group did not change during the experiment. In the AL group, TF latency increased significantly more than baseline during the 30-min period after injection. This was also significantly higher than the latency in the NS group and the L group. In the L group, the TF latency increased significantly above baseline for 20 min after injection and was significantly higher than that in the NS group. Due to the fact that we were able to detect the effect of local anesthesia onset and regression, as well as the local anesthesia continuation action of an additive agent, in rats sedated via an indwelled epidural catheter, we consider our method to be an improvement over conventional methods.

Pharmacological characterization of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel transient receptor potential vanilloid 1 antagonist.

Transient receptor potential vanilloid 1 (TRPV1) activation in peripheral sensory nerve is known to be associated with various pain-related diseases, thus TRPV1 has been the focus as a target for drug discovery. In this study, we characterized the pharmacological profiles of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel TRPV1 antagonist. JTS-653 displaced [(3)H]resiniferatoxin binding to human and rat TRPV1. JTS-653 competitively antagonized the capsaicin-induced activation of human TRPV1 with pA(2) values of 10.1. JTS-653 also inhibited proton-induced activation of human and rat TRPV1 with IC(50) values of 0.320 and 0.347 nM, respectively. Electrophysiological studies indicated that JTS-653 blocked heat-induced inward currents in rat TRPV1 with IC(50) values of 1.4 nM. JTS-653 showed weak or no inhibitory effects on other TRP channels, receptors, and enzymes. JTS-653 significantly prevented capsaicin-induced mechanical hyperalgesia at 1 mg/kg p.o. and attenuated carrageenan-induced mechanical hyperalgesia at 0.3 mg/kg p.o. JTS-653 significantly attenuated carrageenan-induced thermal hyperalgesia at 0.1 mg/kg p.o. and fully reversed at 0.3 mg/kg p.o. without affecting the volume of the carrageenan-treated paw. JTS-653 showed a transient increase of body temperature at 0.3 mg/kg p.o. These results indicated that JTS-653 is a highly potent and selective TRPV1 antagonist in vitro and in vivo and suggested that JTS-653 is one of the most potent TRPV1 antagonists. The profiles of JTS-653, high potency in vivo and transient hyperthermia, seem to be associated with polymodal inhibition of TRPV1 activation.

Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation.

PURPOSE: Systemic carbamazepine, a voltage-gated sodium channel blocker, has been reported to dose-dependently reduce inflammatory hyperalgesia. However, the antinociceptive effects of carbamazepine on the spinal cord in inflammatory conditions are unclear. The aim of the present study was to evaluate the antinociceptive effects of carbamazepine on the spinal cord in a chronic inflammatory condition. METHODS: In Sprague-Dawley rats, a chronic inflammatory condition was induced by complete Freund's adjuvant (CFA) inoculation into the tail. Tail flick (TF) latencies were measured following intraperitoneal carbamazepine, or intrathecal carbamazepine or tetrodotoxin injection in intact rats and in the chronic inflammatory rats. From the values of TF latency at 60 min after drug injection, the effective dose required to produce 50% response (ED(50)) of each drug was derived. RESULTS: Carbamazepine attenuated thermal responses with both systemic and intrathecal administration. The effect was more evident in rats with chronic inflammation than in intact rats; the ED(50s) of intraperitoneal carbamazepine in intact and inflamed rats were 12.39 and 1.54 mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048 nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED(50s) of 1.006 pmol in intact rats and 0.310 pmol in inflamed rats. The relative potencies of intrathecal carbamazepine versus tetrodotoxin for inhibition were approximately 1:150-1:300 in intact and inflamed rats. CONCLUSION: These results indicate that the inhibition of voltage-gated sodium channels, at least tetrodotoxin-sensitive channels, may contribute to the antinociceptive effect of carbamazepine on CFA-induced inflammatory pain, since lower doses of intrathecal carbamazepine and tetrodotoxin attenuated thermal responses to a greater extent in inflamed rats than in intact rats.

[Application of video laryngoscope for vocal cord synechiotomy in a patient with recurrent laryngeal nerve paralysis].

Vocal cord synechia causes respiratory disturbance and severe pneumonia. A 63-year-old woman with recurrent laryngeal nerve paralysis caused by translaryngeal intubation after resection of acoustic tumor and by thyroid surgery in her history and progressive dyspnea, had received vocal cord synechiotomy under general anesthesia. Preoperative endoscopic examination revealed edematous larynx, immobility of left unilateral vocal fold, insufficient mobility of right vocal fold, left arytenoid cartilage dislocation and a posterior glottic adhesion. Anesthesia was induced by propofol administration, and a muscle relaxant was administered following confirmation of effective face mask ventilation. Trachea was cannulated immediately after incision of the scar under indirect video laryngoscopy. Vocal cord synechiotomy was completed without any respiratory complication. The case indicated that recurrent laryngeal nerve paralysis has a potential for vocal cord synechia and difficulty of tracheal intubation, and visibility of the surgical field among anesthesiologists and surgeons by indirect video laryngoscopy for vocal cord synechiotomy contributes to establish prompt surgical manipulation and tracheal intubation as to vocal cord synechiotomy.

Tracheal intubation in a patient with undetectable tracheal narrowing on chest radiography.

We report here a 59-year-old man with a saber-sheath tracheal narrowing who was scheduled to undergo pharyngeal tumor resection under general anesthesia. The tracheal narrowing was not clearly detected by chest radiography during the preoperative examination, but it was visible on axial computed tomography (CT) images taken earlier for diagnostic purposes. Following fiber optic examination of the narrowed segment with the patient under anesthesia, the tube was inserted into the trachea using an Airway Scope. The tube was deliberately advanced into the trachea and was able to pass through the stenosis without any resistance. On postoperative radiological analysis, three-dimensional reconstruction of the trachea and virtual bronchoscopic images revealed a saber-sheath type tracheomalacia located from below the cricoid cartilage to the carina. The membranous wall had a normal width. This case indicates that chest radiographs may occasionally be inadequate for evaluating asymptomatic patients with tracheomalacia. If CT images have been taken for diagnostic purposes, they should be examined together with the chest radiograph. Digital chest radiography with edge enhancement may become a useful tool in the preoperative detection and evaluation of undetectable tracheal narrowing on conventional chest films.

Transient lower limb pain following accidental thoracic subarachnoid insertion of an epidural catheter.

Transient sensory disturbances, including dysesthesia or neurologic deficits in the lower extremities or buttocks have been described as complications of neuraxial anesthesia. We report a case of transient lower limb pain following the accidental placement of an epidural catheter into the thoracic subarachnoid space. A 31-year-old woman was scheduled to undergo laparoscopic myomectomy. An epidural catheter was accidentally inserted subarachnoid at the T12-L1 intervertebral space with a 2-ml test dose of 2% lidocaine, and was promptly removed. Fulgurant pain and allodynia extending over the L2-5 areas of the left lower limb and buttock started immediately postoperatively. We treated the persistent pain in our patient with epidural infusion of local anesthetics and steroids during her hospital stay, and with carbamazepine and a tricyclic antidepressant after her discharge from the hospital. All signs of allodynia had disappeared on postoperative day 25. Sagittal and axial T2-weighted magnetic resonance imaging (MRI) at the Th12 level revealed a small high-intensity area without mass effect in the ipsilateral dorsal column. The patient's clinical course and MRI diagnosis suggested the inhibition of descending inhibitory pathways resulting from a lesion of the spinal cord as the possible etiology of the transient lower limb pain and allodynia.

[Allergic reaction during anesthesia: two case reports].

We experienced two cases of serious and potentially life-threatening allergic reactions. The first patient was a 28-year-old male patient scheduled for surgery for cerebral arteriovenous malformations and another patient was a 66-year-old male patient scheduled for hepatic resection. After uneventful anesthetic induction, anesthesia was maintained with sevoflurane, air and oxygen. Both patients developed allergic reactions characterized by cardiovascular failure during anesthesia. Resuscitative treatment included rapid fluid infusion, administration of adrenaline and steroid. Both patients were successfully resuscitated without any lasting sequelae. The causative agent in one of these cases was probably a prophylactically used antibiotic, while that of the other case was a reaction to latex. Both patients showed elevated histamine and tryptase concentrations in blood samples. Recently, the incidence of allergic reactions to antibiotics and latex during anesthesia is increasing. Anesthesiologists should, therefore, be aware of the possibility of allergic reactions to all drugs and substances, especially to latex, during the perioperative period.

Suppression of the descending inhibitory pathway by continuous thoracic intrathecal lidocaine infusion reduces the thermal threshold of the tail-flick response in rats.

PURPOSE: For the suppression of descending inhibitory pathways in animals, single-dose lidocaine blockade is reversible and causes less damage than chronic spinal cord injury, decerebration, and cold blockade of the spinal cord. However, single-dose blockade has a variable onset and is relatively short-lived. To surmount these disadvantages, we devised a continuous thoracic intrathecal lidocaine infusion and evaluated its effects in rats. METHODS: Rats were administered continuous intrathecal infusions of 0, 0.25%, 0.5%, and 1% lidocaine at 10 &gml.h(-1) following a 10-&gml bolus. The effects of the continuous thoracic blockade on tail-flick (TF) latency (estimated by the percent maximum possible effect [%MPE]) and on the release of neurotransmitters in the cerebrospinal fluid (CSF) were evaluated. RESULTS: Continuous thoracic blockade with 0.5% and 1% lidocaine infusion reversibly shortened TF latency (%MPE, -22.0 +/- 11.0 % and -21.2 +/- 4.6 %, respectively, versus baseline; P < 0.05) during drug infusion. Compared with normal saline, thoracic intrathecal infusion of lidocaine significantly lowered norepinephrine and serotonin concentrations in the CSF at 1 h of infusion (P = 0.02 for both). CONCLUSION: Continuous thoracic blockade by local anesthetic resulted in reversible suppression of descending inhibitory pathways for varying durations. Such blockade may provide further information regarding nociceptive transmission and the mechanisms of antinociception in animals.

Three-dimensional CT image analysis of a tracheal bronchus in a patient undergoing cardiac surgery with one-lung ventilation.

The incidence of a tracheal bronchus--that is, a congenitally abnormal bronchus originating from the trachea or main bronchi--is 0.1%-2%. Serious hypoxia and atelectasis can develop in such patients with intubation and one-lung ventilation. We experienced a remarkable decrease in peripheral oxygen saturation (SpO2) and a rise in airway pressure during placement of a double-lumen endobronchial tube in a patient with patent ductus arteriosus and tracheal bronchus. Substitution of the double-lumen tube with a bronchial blocker tube provided secure isolation of the lung intraoperatively. A type I tracheal bronchus and segmental tracheal stenosis were identified on postoperative three-dimensional (3D) computed tomographic (CT) images. Preoperative examination of chest X-rays, CT images, and preoperative tracheal 3D images should preempt such complications and assist in securing safe and optimal one-lung ventilation.

Difficult laryngoscopy caused by massive mandibular tori.

Mandibular tori, defined as bony protuberances located along the lingual aspect of the mandible, are a possible cause of difficult intubation. We describe a case of mandibular tori that resulted in difficult intubation. A 62-year-old woman who had speech problems was diagnosed with mandibular tori, and was scheduled for surgical resection. On physical assessment, the patient had a class II Mallampati view and bilateral mandibular tori. Preoperative computed tomography images demonstrated that the bilateral mandibular tori arose from the lingual aspects of the second incisor to the first molar regions of the mandibular corpus, and occupied the floor of the mouth. In the operating room, anesthesia was induced with remifentanil and propofol. After complete paralysis was achieved, laryngoscopy was attempted several times with Macintosh blades. The massive tori prevented insertion of the tip of the blade into the oropharynx, and neither the epiglottis nor the arytenoids could be visualized, i.e., Cormack and Lehane grade IV. Blind nasotracheal intubation was successful and the surgery proceeded uneventfully. The anesthesiologist should examine any space-occupying lesion of the oral floor and should be vigilant for speech problems in order to detect mandibular tori that might impede intubation.

[Case of myocardial infarction during emergency clipping surgery of a cerebral aneurysm].

An 80-year-old woman with subarachnoid hemorrhage underwent emergency neck clipping of a cerebral aneurysm. She had previously undergone surgery for an abdominal aortic aneurysm 10 years before. Anesthesia was induced with propofol and maintained with a combination of fentanyl and sevoflurane (0.5-1.5%) in air and oxygen. Ventricular fibrillation occurred immediately before clipping of the aneurysm, in the absence of preexisting myocardial ischemia, and recurred 4 times thereafter during the surgery. The ventricular fibrillation was successfully treated with cardioversion. We administered catecholamines, nitrates, calcium antagonists, nicorandil and heparin, following which the patient's hemodynamics gradually improved. After the operation, the patient was transferred to the cardiovascular center of a neighboring university where she successfully underwent emergency percutaneous transluminal coronary angioplasty. The patient was discharged from hospital 10 days later without any complications. Patients undergoing vascular surgical procedures or having a preoperative history of prior vascular surgery are at high risk for perioperative myocardial infarction. It is necessary to perform cardiac examination, including coronary angiography, preoperatively in such patients, even in those who are otherwise asymptomatic.

[Compression of a nasotracheal tube in the nasal cavity of a patient with craniofacial fibrous dysplasia].

A 42-year-old woman with craniofacial fibrous dysplasia underwent osteoplasty of maxillary and mandibular bone. Preoperative CT images showed osteosclerosis and ground glass appearance of the right side of the skull including the orbit, temporal bone, paranasal sinus, and maxillary and mandibular bones, as well as hypertrophy of the nasal septum. Inhalation anesthesia was induced and 8.0-mmID polyvinyl chloride endotracheal tube was inserted via the left nostril with slight resistance. At emergence, a 10-Fr suction catheter could not be passed throgh the tube but an 8-Fr nasogastric tube could be passed. A part of the tube positioned in the nasal cavity was apparently compressed. Preoperative examination of the nasal cavity and nasal septum using CT or MRI may be desirable for nasotracheal intubation in the patients with craniofacial tumor, and the application of a spiral reinforced endotracheal tube may contribute to prevent such cases of airway obstruction in the nasal cavity.

The effect of Sub-MAC anesthesia and the radiation setting on repeated tail flick testing in rats.

The tail flick (TF) response is regarded as a spinal reflex that is influenced by supraspinal structures. The TF test using radiant heat is the most common way to assess pain perception; however, there are few reports dealing with the heat source's properties and score consistency. This study examined the usefulness of light anesthesia for suppressing supraspinal signals and the effects of radiant heat on skin temperature during TF testing. The fluctuations of TF latency over one hour were evaluated while the rats were given oxygen and 0%, 0.5%, 1.0%, or 1.5% isoflurane. The stimulator's infrared radiant (IR) power flux was measured over time, and the tail skin surface temperature was predicted using a non-linear regression equation. TF latencies were measured at various heat source intensities, and response temperatures were estimated. Inhalation anesthesia suppressed the TF reflex according to the inspiratory concentration of the volatile anesthetic. IR power fluxes reached constant power 2.5 s after the stimulator was turned on, and the predicted skin temperature depended on the maximum IR power flux of the IR intensity and the radiation time. One percent isoflurane inhalation and an IR20 heat intensity (which was 161.5 mW/cm(2) and resulted in a skin temperature of 65 degrees C after 10 s of radiation) provided reliable TF latencies on repeated TF testing. Given these results, it can be concluded that the stimulator setting influenced TF latency, and that the inhalation of light anesthesia provided consistent scores on repeated TF testing.

[How much should be done for better thromboprophyraxis?].

How much should be done for better managements of the perioperative thromboprophylaxis? In Japan, the guideline for prevention of venous thromboembolism (VTE) was established for the first time in February, 2004. Our academic medical center formed a committee for prevention of thrombosis for all departments using operating rooms in October, 2002 and began to make the database of symptomatic pulmonary thromboembolism (PTE). From the end of September, 2003, we asked the surgeons to indicate the PTE risk grades when ordering surgical operations. The prevention team of VTE prepared VTE risk tables and recommended prevention methods for perioperative period. If surgeons did not choose prevention methods, the team took the consultation. Also, we made a manual how to make emergency calls and a flow chart for the diagnosis and therapy cooperating with cardiologists and anesthesiologists. We founded another meeting of Kinki Clinical Thrombosis Research Association for the study and education. We assessed the incidence of symptomatic PTE every year. The incidences of symptomatic PTE were 14 of 4101 (0.34%) in the first year, 2 of 3796 (0.053%) in the second year; 2 of 4002 cases (0.049%) in the third year under general anesthesia, respectively. Cases of fatal PTE were 2 (0.34%), 1 (0.049%) and 0 (0%), respectively. The multidisciplinary thromboprophylaxis effort that we had adopted was very important to prevent aggravation of VTE.

[Central hypotensive effect involving neurotransmitters of long-term administration of taurine to stroke-prone spontaneously hypertensive rat].

BACKGROUND: Taurine is an inhibitory neurotransmitter or neuromodulator that reduces blood pressure when systemically or centrally administered. We studied the central hypotensive effects of long-term oral taurine administration. METHODS: Arterial blood pressure was measured after delivering an intracisternal injection of 100 mg x 20 microl(-1) or 200 microg x 20microl(-1) of taurine in normal saline, or 20 micro1 normal saline to anesthetized Sprague-Dawley rats. Drinking water containing 3% taurine was administered to stroke-prone spontaneously hypertensive rats (SHRSP) from the age of 4 weeks. Amino acids and monoamine neurotransmitters in the cerebrospinal fluid were measured at 8, 12, 16, 18 weeks of age in taurine treated SHRSP and normotensive Wistar Kyoto rats (WKY) and in untreated SHRSP using high performance liquid chromatography. RESULTS: Intracisternal injections of taurine caused a dose dependent decrease in arterial blood pressure. Although concentrations of taurine decreased in treated SHRSP rats in an age-related manner, the drug persistently suppressed the development of hypertension. The values of excitatory amino acids and GABA, norepinephrine, NMN, dopamine metabolites, serotonin and its metabolite were lower in taurine-treated SHRSP than those in untreated SHRSP. CONCLUSIONS: Taurine reduces blood pressure through not only direct inhibition of the cardiovascular center in the medulla, but also by reducing brain monoamine concentrations.

[Alteration of neurotransmitters in the cerebrospinal fluid in SHRSP rats due to long-term administration of clonidine].

BACKGROUND: Clonidine, an alpha2-adrenoreceptor and imidazoline L receptor agonist, is commonly used in the treatment of hypertension. We evaluated the central hypotensive effect of long-term oral administration of clonidine. METHODS: Clonidine was administered to stroke-prone spontaneously hypertensive rats (SHRSP) of four to twenty weeks of age. Cerebrospinal fluid (CSF) was collected via the cisterna magna every two weeks, from eight weeks of age, from clonidine treated SHRSPs, age-matched normotensive Wistar Kyoto (WKY) rats and un-treated SHRSPs. Amino acid neurotransmitters and monoamine neurotransmitters in the samples were measured by high performance liquid chromatography with electro-chemical detectors. RESULTS: The levels of norepinephrine, dopamine and serotonin were significantly higher, while taorine was significantly lower in the SHRSPs than in WKY rats. Long-term clonidine administration decreased the levels of norepinephrine, dopamine, serotonin, GABA and taurine. The levels of excitatory amino acids, however, were unaffected by clonidine administration. The levels of metabolites of norepinephrine increased, but those of dopamine and serotonin decreased. CONCLUSIONS: These results suggest that the presynaptic inhibition of norepinephrine release from norepinephrine neurons, accompanied by postsynaptic inhibition of excitatory and inhibitory neurons modulate clonidine-induced hypotension.