Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function / 中国针灸

OBJECTIVE@#To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function.@*METHODS@#A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated.@*RESULTS@#After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05).@*CONCLUSION@#Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Effect of acupuncture and estazolam on episodic memory and sleep structure in patients with chronic insomnia disorder: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the effect on chronic insomnia disorder (CID) and influences on episodic memory and sleep structure between acupuncture and estazolam tablets.@*METHODS@#A total of 140 CID patients were randomized into a meridian-point group (46 cases, 1 case dropped off), a non-meridian-and-non-acupoint group (47 cases, 2 cases dropped off) and a medication group (47 cases, 2 cases dropped off). In the meridian-point group, Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6) and Shenmai (BL 62) were selected and the routine acupuncture was applied. In the non-meridian-and-non-acupoint group, the needling technique was same as the meridian-point group. Acupuncture was given once daily for 4 weeks in the above two groups. In the medication group, estazolam tablets were administered orally, taken 1 to 2 mg per night, consecutively for 4 weeks. Before and after treatment, the changes in the following indexes were observed in each group, i.e. the score of insomnia severity index (ISI), the score of auditory verbal memory test (AVMT) and the relevant indexes of sleep structure [total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE) and the percentage of non rapid eye movement phase 1, 2 and 3 (N1, N2 and N3) and rapid eye movement time (REM) in TST].@*RESULTS@#After treatment, ISI scores were reduced in the meridian-point group and the medication group (<0.01), the score in the meridian-point group was lower than the medication group and the non-meridian-and-non- acupoint group respectively (<0.01) and that in the medication group was lower than the non-meridian-and-non-acupoint group (<0.01). After treatment, the score of each of immediate recall, short-term delayed recall, long-term delayed recall and delayed recognition of AVMT was increased in the meridian-point group and the medication group respectively (<0.01, <0.05) and the score of each item of AVMT in the meridian-point group was higher than the medication group and the non-meridian-and-non-acupoint group respectively (<0.01, <0.05). The scores of immediate memory and delayed recognition in the medication group were higher than the non-meridian-and-non-acupoint group respectively (<0.01). After treatment, SOL, WASO and N1% were all reduced (<0.01) and TST, SE, N3% and REM% were all increased (<0.01, <0.05) in the meridian-point group and the medication group, N2% in the meridian-point group was reduced (<0.01). After treatment, N1% and N2% in the meridian-point group were lower than the medication group (<0.01) and N3% and REM% were higher than the medication group (<0.01). After treatment, TST, SE and N3% in the meridian-point group and the medication group were all higher than the non-meridian-and-non-acupoint group respectively (<0.01, <0.05) and SOL, WASO and N1% were lower than the non-meridian-and-non-acupoint group respectively (<0.01). REM% in the meridian-point group was also higher than the non-meridion-and-non-acupoint group (<0.01), and N2% in the meridian-point group was also lower than the non-meridian-and-non-acupoint group (<0.01).@*CONCLUSION@#Compared with estazolam, acupuncture much better improves sleep quality and episodic memory in patients with chronic insomnia disorder, which is possibly related to the regulation of sleep structure of patients in treatment with acupuncture.

acupuncture on refractory insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the therapeutic effect of acupuncture, conventional acupuncture and oral estazolam tablet on refractory insomnia.@*METHODS@#A total of 180 patients with refractory insomnia were randomized into a acupuncture group, a conventional acupuncture group and a medication group, 60 cases in each group. In the acupuncture group, acupuncture was applied at Baihui (GV 20), Waiguan (TE 5), Neiguan (PC 6), Weishu (BL 21), Zhongwan (CV 12) and Taixi (KI 3); in the conventional acupuncture group, conventional acupuncture was applied at Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) and Anmian (Extra). Supplementary acupoints were added according to different patterns in the two acupuncture groups, and the treatment was given once a day, 7 times as one course and 4 courses were required. In the medication groups, estazolam was taken orally 1 h before sleep, 1 mg each time, once a day for 4 weeks. The Pittsburgh sleep quality index (PSQI) score was observed before and after treatment and the therapeutic effect was evaluated in the 3 groups.@*RESULTS@#The total effective rates in the acupuncture group and the conventional acupuncture group were 90.0% (54/60) and 83.3% (50/60), which were superior to 30.0% (18/60) in the medication group (both <0.05). Compared before treatment, the PSQI scores were significantly reduced in the two acupuncture groups (all <0.05), the sleep efficiency and the total score of PSQI were reduced in the medication group (both <0.05). After treatment, the changes of sleep latency, sleep efficiency, sleep disorder, daytime function and total score of PSQI in the acupuncture group were significantly larger than those in the conventional acupuncture group (all <0.05). The changes of PSQI scores in the acupuncture group were significantly larger than the medication group (all <0.05). The changes of sleep quality, sleep latency, sleep time, sleep disorder, daytime function and total score of PSQI in the conventional acupuncture group were significantly larger than the medication group (all <0.05).@*CONCLUSION@#The therapeutic effect of acupuncture on refractory insomnia is superior to estazolam and conventional acupuncture.

Subacute insomnia treated with 's three-promotion needling method: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the differences in the sleep quality and the effects on insomnia severity between 's three-promotion needling method and the oral administration of estazolam.@*METHODS@#A total of 70 patients of subacute insomnia were randomized into a three-promotion needling group and a medication group, 35 cases in each one. In the three-promotion needling group, the mild promotion technique with the filiform needle, the warm promotion technique with the fire needle and the strong promotion technique with the three-edged needle were adopted in combination. The acupuncture with the filiform needle was used at Baihui (GV 20), Sishencong (EX-HN1), Shenting (GV 24), Shenmen (HT 7), etc, The treatment was given 3 times a week, once every 2 days. The pricking technique with fire needle was applied to Ganshu (BL 18), Xinshu (BL 15), Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23) and Geshu (BL 17), once every 3 days, twice a week. The bleeding technique with the three-edged needle was used at the ear apex, once every 2 days, 3 times a week. In the medication group, the estazolam tablets were taken orally before sleep, 1mg once every 2 days. The treatment was given consecutively for 4 weeks in the two groups. Separately, before treatment, in 2-week treatment and in 4-week treatment as well as in 1-month follow-up after treatment, the Pittsburgh sleep quality index (PSQI) and the insomnia severity index (ISI) scores were recorded in the patients of the two groups. The clinical effects were evaluated in the two groups.@*RESULTS@#In 2 weeks and 4 weeks of treatment, as well as in the follow-up, PSQI scores and ISI scores were all reduced obviously as compared with those before treatment in the two groups (all <0.05). In the three-promotion needling group, the PSQI score at each time point was reduced much more obviously as compared with the medication group (all <0.05). In the follow-up, the ISI score in the three-promotion needling group was lower than the medication group (<0.05). The total effective rates were 97.2% (34/35) and 91.4% (32/35) at the end of treatment and in the follow-up respectively in the three-promotion needling group, higher than 85.7% (30/35) and 71.4% (25/35) in the medication group (both <0.05).@*CONCLUSION@#'s three-promotion needling method much more effectively improves the sleep quality and reduces insomnia severity in the patients of subacute insomnia. This therapy presents the satisfactory short-term and long-term effects.

"Governor vessel method of acupuncture" combined with estazolam for insomnia: a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To compare the clinical efficacy differences between "governor vessel method of acupuncture" combined with estazolam and estazolam alone for insomnia.</p><p><b>METHODS</b>Seventy patients of insomnia were randomly divided into an observation group and a control group, 35 cases in each one. The patients in the control group were treated with oral administration of estazolam, 2 mg each time; the estazolam was taken 30 min before sleeping. The patients in the observation group were treated with "governor vessel method of acupuncture" combined with estazolam; the positive reaction points along governor vessel and Baihui (GV 20) were selected as the main points. The acupuncture was given for 30 min per treatment, once every two days. Both groups were treated for four weeks. Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were observed before and after treatment. Clinical efficacy was assessed between the two groups and adverse reactions were recorded.</p><p><b>RESULTS</b>The total effective rate was 94.3% (33/35) in the observation group, which had no significant difference with 82.9% (29/35) in the control group (>0.05). The cured and markedly effective rate was 71.4% (25/35) in the observation group, which was superior to 42.9% (15/35) in the control group (<0.05). Each item score and total score of PSQI were decreased obviously after treatment in the observation group (all <0.05), while the score of sleep latency, sleep duration and sleep efficiency as well as total score of PSQI were decreased obviously after treatment in the control group (all <0.05). The scores of sleep duration, sleep disturbance and day dysfunction due to sleepiness as well as total score of PSQI in the observation group were lower than that in the control group (all <0.05). After treatment, the PSG-related parameters of total sleeping duration, sleeping latency, sleeping arousal and sleeping efficiency were improved significantly in the observation group (all <0.05); the total sleeping duration, sleeping arousal and sleeping efficiency were also improved in the control group (all <0.05). The total sleeping duration, sleeping latency, sleeping arousal and sleeping efficiency in the observation group were superior to those in the control group (all <0.05). 4 adverse reactions in the observation group and 3 adverse reactions in the control group were observed.</p><p><b>CONCLUSION</b>"Governor vessel method of acupuncture" combined with estazolam could significantly improve insomnia, which are superior to estazolam alone.</p>

Senile insomnia treated with integrated acupuncture and medication therapy: a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To compare the efficacy difference in the treatment of senile insomnia among western, medication, acupuncture and the integrated therapy of acupuncture and western medication.</p><p><b>METHODS</b>Ninety-eight patients of senile insomnia were randomized into a western medication group (30 cases), an acupuncture group (35 cases) and an integrated acupuncture and medication group (35 cases). In the western medication group, estazolam 1mg was prescribed, taken 30 min before going to bed, oryzanol 20 mg, oral administration, three times a day, for 4 weeks totally. In the acupuncture group, the simple acupuncture therapy was applied at Shenmen (HT 7), Sanyinjiao (SP 6), Anmian (Extra), Baihui (GV 20) and Sishencong (EX-HN 1), as well as the supplementary points selected according to the differentiation. The acupuncture treatment was given once a day, 5 treatments a week, for 4 weeks totally. In the integrated acupuncture and medication group, the western medication was combined with acupuncture. The dosage and usage of western medication were same as those in the western medication group; and acupoints in acupuncture treatment were same as those in the acupuncture group. The treatment lasted for 4 weeks in the three groups. Pittsburgh sleep quality index (PSQI) and clinical efficacy were observed before treatment, after 4 weeks' treatment and in 4 weeks after discontinuity of treatment in the three groups.</p><p><b>RESULTS</b>Four weeks after treatment, the clinical curative rates were 3. 3% (1/30), 21. 2% (7/33) and 25. 7% (9/35) in the western medication group, the acupuncture group and the integrated acupuncture and medicines group separately. The total effective rates were 70. 0%(21/30), 93. 9%(31/33) and 97. 1%(34/35) in the three groups separately. The curative rates and the total effective rates in the integrated acupuncture and medication group and the acupuncture group were higher than those in the western medication group separately (all, P<0. 01). PSQI scores after 4 Weeks' treatment were all improved as compared with those before treatment in the three groups (all P<0. 05). PSQI score in either the integrated acupuncture and medication group or the acupuncture group was lower than that in the western medication group, indicating the significant difference (both P< 0. 05). Four weeks after discontinuity of treatment, the efficacy was stable in the acupuncture group and the integrated acupuncture and medication group. PSQI score did not change as compared with that in the 4th week of treatment. The score in the western medication group ran back, close to that before treatment (P>0. 05). During the treatment, a few patients had dry mouth in the western medication group. The adverse reactions were not discovered in the other two groups.</p><p><b>CONCLUSION</b>The integrated therapy of acupuncture and medication achieves the quick efficacy on senile insomnia and rapidly relieves the symptoms, with quite high clinical curative rate and total effective rate obtained. The long-term efficacy is better than that of western medication. The integrated therapy is the first option among the three therapeutic programs.</p>

Stability of estazolam in dog tissues preserved in formaldehyde solution / 法医学杂志

OBJECTIVE@#To investigate the stability of estazolam in biological samples preserved in formaldehyde solution.@*METHODS@#The dog was given intragastric administration of estazolam with a dose of 37.6 mg/kg and killed 2 h later. Heart, liver, kidney and brain of the dog were cut up into 1 g and preserved in 4% formaldehyde solution respectively. The content of estazolam in biological samples and formaldehyde solution were analyzed by HPLC at different times.@*RESULTS@#The content of estazolam in heart, liver, kidney and brain or in formaldehyde solution reduced gradually followed with the extention of preservation time. At the 63rd day, estazolam content in four tissues were 0.8%, 1.7%, 1.0% and 2.2% of the original content respectively.@*CONCLUSION@#Estazolam in tissues can diffuse into formaldehyde solution and decomposed quickly, so biological samples contained estazolam should not be preserved in formaldehyde solution.

The influence of estazolam on human neurobehavioral function / 法医学杂志

OBJECTIVE@#To study the relation between human blood estazolam concentration and neurobehavioral function.@*METHODS@#The neurobehavioral ability of 10 volunteers were measured with computer-administered neurobehavioral evaluation system-chinese3 (NES-C3) and SMART EquiTest system.@*RESULTS@#The neurobehavioral ability and balance function declined 1 h later after dosing estazolam. The neurobehavioral ability index and balance function declined to the lowest level 3 h later after dosing estazolam. The neurobehavioral ability recovered partly 6 h later after dosing estazolam, and neurobehavioral ability recovered completely 10 h later.@*CONCLUSION@#Driving ability was impaired when estazolam concentration in blood is 20 ng/mL, and the neurobehavioral ability declined when estazolam concentration is 40 ng/mL in blood. The influence to human in absorption process is greater than the metabolic process with the same estazolam concentration.

Analysis on somnipathy related factors in elderly patients with stroke and comparative study on the efficacy of treatment by traditional Chinese medicine and by estazolam / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To analyze the somnipathy related factors in elderly patients with stroke and to compare effects of traditional Chinese medicine and estazolam on sleep and the followed nervous function.</p><p><b>METHODS</b>The somnipathy related factors in 336 elderly patients with stroke, 221 accompanied with somnipathy and 115 with normal sleep, were studied and analyzed. Moreover, the 221 patients with somnipathy were assigned to two groups, 112 in the treated group treated with TCM according to syndrome differentiation, and 109 in the control group treated with estazolam. Changes of scores rated by neurological deficit scale (NDS), sleep dysfunction rating scale (SDRS), Hamilton anxiety rating scale (HAMA), Hamilton depression scale (HAMD), and treatment emergent symptom scale (TESS) were observed before and after treatment.</p><p><b>RESULTS</b>The occurrence of somnipathy in patients with cerebral hemorrhage was significantly higher than in those with cerebral infarction; it was higher in patients with lesion in brain stem, cerebral hemisphere (frontal lobe), or basal ganglion than in those with lesion in other sites; and patients with severe neurological deficit were more liable to having somnipathy. TCM showed a significant effect in improving the insomnia symptoms in patients, with the total effective rate reaching 81.25% (91/112), which was higher than that in the control group, 65.14% (71/109, P < 0.01). Along with the improving of sleep, marked recovery of the nervous function was shown in both groups, with NDS score reduced significantly (P < 0.05).</p><p><b>CONCLUSION</b>The occurrence of somnipathy in stroke patients was closely related with the property and site of lesion, and the neurological deficit degree of patients. Better sleep is surely favorable for recovery of the nervous function, and TCM shows a favorable efficacy on somnipathy.</p>

Effect of modified xiaoyao powder for improving sleep in patients with psychological stress insomnia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To subjectively and objectively assess the effect of Jiawei Xiaoyao Powder (JXYP) on sleep in patients with psychological stress insomnia. METHHODS: A randomized controlled study was conducted in 33 patients with psychological stress insomnia. They were assigned to 4 groups, 4 in the TCM group treated with JXYP, 5 in the Western medicine (WM) group treated with Estazolam, 9 in the integrated medicine (IM) group treated with JXYP plus Estazolam, and 10 in the control group treated with placebo. Quality of sleep in patients was assessed subjectively and objectively before treatment and 6 weeks after treatment by Pittsburgh sleep quality index (PSQI), self-rating scale of sleep (SRSS) and polysomnography (PSG), respectively.</p><p><b>RESULTS</b>Subjective assessment on sleep showed that after 6-week treatment, the scores of PSQI and SRSS remarkably reduced in the TCM, IM and control groups (P < 0.05), while the decrease was insignificant in the WM group (P > 0.05), but no significant difference between groups was shown. The objective assessment by PSG showed that no significant change was found after treatment in parameters of total sleep time (TST), sleep time of phase 1 and 2, slow wave phase, rapid-eye-movement (REM) phase, sleep latency, REM sleep latency, also in long waking and short waking times in all group (P > 0.05), but a significant increase of sleep efficacy (P < 0.05) and an increasing trend of TST (P > 0.05) were shown in the IM group, and an increasing trend of both in the TCM group (P > 0.05).</p><p><b>CONCLUSION</b>JXYP, combined with or without Estazolam, can improve the quality of sleep subjectively, and the combination of the two could enhance the efficacy of sleep in patients with psychological stress insomnia.</p>

Comparative study on treatment of somnipathy in patients with hypertension by traditional Chinese medicine and by estazolam / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the efficacy of traditional Chinese medicine (TCM) in treating somnipathy in patients with hypertension, and to observe the change of blood pressure after sleep being improved.</p><p><b>METHODS</b>Two hundred and thirty-nine patients with hypertension accompanied somnipathy were randomly assigned to two groups, 123 patients in the treated group were treated with TCM according to syndrome differentiation, and 116 in the control group treated with Estazolam. Changes of blood pressure, scores of sleep dysfunction rating scale (SDRS), Hamilton anxiety rating scale (HAMA) and treatment emergent symptom scale (TESS) before and after treatment were observed.</p><p><b>RESULTS</b>TCM showed a significant effect on hypnagogic disturbance, and significantly reduced the scores of insomnia syndromes in early sleep stage, improve the quality of sleep, prolong the sleeping time to fulfill the physiological requirement, the total effective rate being 80.5% (99/123 cases), with the overall effect higher than that (66.4%, 77/116 cases) in the control group (P < 0.05). Along with the improving of sleep, blood pressure, both systolic and diastolic, reduced in both groups, but with the reduction in the treated group superior to that in the control group (P < 0.01), and the rate of reaching target BP (< 140/90 mmHg) in the former was also significantly higher than that in the latter (39.7%, 46/116 cases, P < 0.05). As compared with those in the control group, the occurence of adverse reaction, were less in the treated group (P < 0.05).</p><p><b>CONCLUSION</b>TCM has better efficacy in treating somnipathy of hypertension patients than Estazolam. And the improvement of somnipathy is favorable for improving the hypertensive condition of patient.</p>

Analysis of 37 drugs in whole blood by HPLC after solid phase extraction / 法医学杂志

OBJECTIVE@#To develop a specific, sensitive, reproducible SPE-HPLC method for the determination of 37 drugs in whole blood.@*METHODS@#With the doxapram as internal standard, Oasis column was used to extract drugs from whole blood. Two kinds of mobile phases were used in this study. Separations were achieved by a LiChrospher 100 RP-C18 (250 mm x 4.0 mm x 5 microm) column kept at 50 degrees C, the DAD detector was set at 230 nm and 250 nm.@*RESULTS@#The limit of detection were 1-30 ng/mL. The method showed excellent linearity and the linear correlation coefficient was > or =0.997 98. The relative standard deviation for between-day and within-day assay were <10%.@*CONCLUSION@#The method is effective, simple, reliable and has been used in real cases.

Effects of midazolam and estazolam as hypnotics in hypertensive patients with chronic insomnia: a multicentre, open labeled, randomized clinical trial / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the safety and efficacy of midazolam and estazolam in hypertensive patients with chronic insomnia.</p><p><b>METHODS</b>In this multicentre, open labeled, randomized clinical trial, 217 adult (18 - 75 years) hypertensive patients (BP range 140 mm Hg <or= SBP < 180 mm Hg, DBP < 110 mm Hg) with chronic insomnia (>or= 3 times/week for more than 1 month) were randomly divided into midazolam (7.5 - 15 mg before sleep, n = 113) or estazolam group (1 - 2 mg before sleep, n = 104). Patients took medication according to own need. Sleep diary should be completed within 15 minutes after getting up next morning. Follow-up analysis was performed in patients completed 8 sleep diaries or received midazolam or estazolam for 1 month. Patients' sleep diaries were evaluated, blood pressure and heart rate before and after therapy were measured and adverse events were recorded.</p><p><b>RESULTS</b>(1) Blood pressure was equipotent reduced after both treatments (-11.8/7.3 mm Hg for midazolam group, and -9.1/5.6 mm Hg for estazolam group, all P < 0.05 vs. before treatment). (2) The total sleep score was also significantly decreased in both groups after medication (P < 0.01) and midazolam was significantly superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness, but there were no differences in dream frequency and total sleep time. (3) The adverse reactions such as dizziness, headache and nausea was similar in midazolam (3%) and estazolam group (7%, P > 0.05).</p><p><b>CONCLUSIONS</b>It is safe to take midazolam or estazolam for hypertensive patients with chronic insomnia and both drugs reduced blood pressure. Midazolam is superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness.</p>

Identification of estazolam, alprazolam and triazolam in human urine by LC/MSn / 药学学报

<p><b>AIM</b>To investigate the fragmentation behavior of triazolobenzodiazepines and to develop a specific, sensitive and rapid LC/MSn assay for simultaneous determination of estazolam, alprazolam and triazolam in human urine.</p><p><b>METHODS</b>After oral administration of a single 4 mg dose of the drugs to each of three healthy volunteers, urine samples were purified by solid-phase extraction, and then injected into an ODS column (150 mm x 4.6 mm) with a mobile phase of methanol-water (8:2) for LC/MSn analysis. The structures of estazolam, alprazolam and triazolam in human urine were identified by direct comparison of the observed mass spectra and the chromatographic retention time with those of the reference substance. The mass spectrometer (Finnigan LCQ) was operated in positive mode and in two scan modes including SIM and full scan MS/MS mode. The obtained mass spectra was analyzed assisted with the software Mass Frontier 1.0 for their fragmentation pathways.</p><p><b>RESULTS</b>The full scan MS/MS spectra of each compound gave characteristic fragment ions of [M + H - N2]+ and [M + H - Cl]+. The detection limit was below 0.5 ng.mL-1 for estazolam, alprazolam and triazolam in human urine.</p><p><b>CONCLUSION</b>The method is useful in forensic and clinical toxicology in which unequivocal identification of eatazolam, alprazolam and triazolam is desired.</p>

Nuevas Benzodiazepinas / New Benzodiazepines

En el último decenio han aparecido en nuestro mercado cuatro benzodiazepinas, ellas podrían representar avances sutiles pero importantes en el tratamiento de los desórdenes de ansiedad y del insomnio. En este trabajo se revisa brevemente la farmacología, la farmacocinética y las características clínicas de este grupo para facilitar su mejor manejo por el médico. Además, se presenta someramente algunas perspectivas futuras.

Estudo multicentrico com um novo benzodiazepinico hipno-indutor - estazolam - em insonia. / Multicenter study with a new hypnotic benzodiazepinic inducer - estazolam - in insomnia

Sao descritos os resultados de um estudo multicentrico com um novo hipnotico benzodiazepinico - estazolam. A analise inclui 677 pacientes com insonia concomitante a quadros psiquiatricos (predominancia de transtornos neuroticos e razoavel incidencia de quadros psicoticos) e a doencas clinicas variadas (predominancia de disturbios cardiocirculatorios e neurologicos). Na opiniao dos medicos, a insonia em relacao a admissao estava melhorada ou muito melhorada em 87,7% dos pacientes, apos 10 dias de tratamento e em 94,4% dos pacientes, apos 20 dias de tratamento. As queixas atribuidas pelos pacientes ao tratamento nao constituiram obstaculo a sua continuacao, seja pela escassa incidencia, seja por seu grau leve na maioria dos casos. Estazolam mostrou-se um recurso terapeutico eficaz e seguro para insonia

Estudio controlado doble ciego de estazolam en el tratamiento del isomnio / Double-blind controlled study with estazolam in treatment of insomnia

Se llevo a cabo un estudio controlado doble ciego, con 24 voluntarios que padecian insomnio, los cuales fueron tratados con un nuevo hipnotico-sedante; triazolobenzodiacepinico (estazolam) para determinar su efecto en el insomnio y como inductor del sueno administrado la noche anterior a una intervencion quirurgica. En este estudio, que tuvo duracion de 14 dias, se comparo el estazolam de 1g (grupo IE) o de 2g(grupo 2E) con fluorazepam 15 mg (grupo 15F).El estazolam no produjo hipnosis continua ni produjo accion de rebote despues de retirar la droga, tampoco produjo cambio en el funcionamiento cardiovascular o depresion respiratoria.La tolerancia fue excelente, siendo um magnifico hipnotico a la dosis empleada