No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study

Background Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient. Methods In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of “compound reserpine and triamterene tablets (CRTTs)” for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected. Results From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users (P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users. Conclusions There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered;and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

Pramipexole, a dopamine D3/D2 receptor-preferring agonist, attenuates reserpine-induced fibromyalgia-like model in mice

Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.

Toward Total Synthesis of Yohimbine and Reserpine Alkaloids;Part 1.An Improved Synthesis of cis-5,8-Dihydroxy-1,4,5,8,9,10-hexahydronaphthalene-1,8-lactone via Selective Reduction of the Conjugated Ketone with Zn(BH_4)_2

An improved and high-yielding synthesis of cis-5, 8-dihydroxy-1, 4, 5, 8, 9, 10- hexa- hydronaphthalene-1,8-lactone 7, an intermediate for (-)-reserpine 1 is presented. The conjugated ketone 5 was regioselectively reduced to afford lactone 7 with zinc borohydride formed in situ from KBH4 and ZnCl2 in THF.

A Novel Flow Injection Chemiluminescence System for the Determination of Reserpine

A novel flow injection cheminescence (FICL) system for the determination of reserpine is presented in this paper. It is based on the CL reaction of reserpine, IO - 4 and H 2O 2 in H 2SO 4 medium. The CL intensity was correlated with concentration of reserpine in the range of 1.0×10 -6～1.0×10 -4 g/mL with a detection limit of 1.35×10 -7 g/ mL. The relative standard deviation is 2.63% for 11 measurements of 2×10 -5 g/mL reserpine standard solution. The method has been applied to the determination of reserpine in pharmaceutical preparations and the results are in good agreement with that of the standard method.

Reserpine Improves Working Memory

Despite exhaustive search, no drug is in sight for AD. Earlier, we reported that reserpine, an antihypertensive and antipsychotic drug, ameliorates Amyloid beta (Aβ-AD causing peptide) toxicity and confers several positive enhancements in the C. elegans model system. Here, we evaluate whether reserpine can provide protection against working memory and against AD in the mouse model. Reserpine (0.08 mg) was administered orally on alternate days to the non-Tg and accelerated Aβ deposition (at 2 months of age)and cognitive deficit (4 months of age) developing 5XFAD AD Tg mouse model expressing mutant human APP (3 familial mutations) and human Presenilin1(2 familial mutations) in the neurons, and follow their working memory for 2 months using the spontaneous Y-maze alteration behavioral paradigm. Reserpine enhanced working memory in non-Tg mice and improved the cognitive deficit in the 5XFAD AD Tg mice. Hence, reserpine can be considered for a detailed evaluation in the 3X Tg AD mouse model and a pilot study in AD patients.

Reserpine-Induced Progressive Parkinsonism in Mice Predisposed and Non-Predisposed to Depressive-Like Behavior

Parkinson’s disease (PD) is a progressive degenerative condition that mainly affects the elderly. The disease comprises motor symptoms such as tremors at rest, loss of voluntary movement, decreased muscle strength, propensity to lean forward and acceleration of the walking pace. These signs are related to the degeneration of the nigrostriatal dopaminergic pathway. Patients also have non-motor symptoms, among which sleep alterations, cognitive deficits, fatigue, pain and depression stand out. Although depression has been described as the most prevalent non-motor symptom, it is not clear whether this mood disorder is due to PD or patients would already have a greater predisposition. The present study evaluated the relationship between the predisposition to depressive-like behavior and the development of motor alterations in a progressive pharmacological model of PD in mice. Mice were classified into groups of depressive-like propensities and submitted to the pharmacological model. Reserpine was administrated at 0.1 mg/kg on alternate days for 40 days. The catalepsy and oral movement tests were used to evaluate motor alterations, the sucrose preference test was used to evaluate anhedonia, and the open field test was applied to evaluate general activity. Reserpine promoted parkinsonian motor impairments, and there were no differences between animals from different depressive-like behavior profiles. Thus, it was not possible to find a relationship between parkinsonism and the propensity to depression based on the basal sucrose preference test. More studies with other evaluations of depressive-like behavior are needed to confirm the results found in our study.

Flow-injection Chemiluminescence Determination of Reserpine in Medicine and Biological Fluids with Controlled-Reagent-Release Technology

A sensitive and rapid chemiluminescence (CL) flow injection with controlled reagent release technology for the determination of reserpine was proposed. The CL reagents, luminol and dichromate, used in this sensor, were all immobilized on anion exchange resin. Through injection of 100 μL of water, the reagents on the anion exchange resin column were eluted and in the presence of reserpine, the CL intensity was decreased, by which reserpine could be sensed. Reserpine was quantified by measuring the decrement of CL intensity, which was observed linear with the logarithm of reserpine concentration in the range of 1 0-500 0 ng/mL, and the limit of detection was 0 4 ng/mL (3 σ ) with a relative standard deviation of less than 3 0%. The proposed procedure was applied in the assay of reserpine in pharmaceutical preparation and biological fluids without any pre treatment process and with sampling frequencies of 72 times per hour.

Inhibitory effects of reserpine and carbonyl cyanide m-chloro-phenylhydrazone on fluoroquinolone resistance of Acinetobacter baumannii

Mechanisms of bacterial resistance to fluoro-quinolones may be grouped intothree principal categories: gene mutations of DNA topoisomerase Ⅱ (GyrA or GyrB), DNA topoisomeraseⅣ ( ParC or ParE), decrease of outer membrane permeation and upregulation of multi-drug effluxpump (active efflux system). Efflux pumps are transport proteins removing toxic substrates(including virtually all classes of clinically relevant antibiotics) from cells to the externalenvironment. These proteins exist in both Gram positive bacteria and Gram negative bacteria as wellas in fungi and mammalian (tumour) cells. It has been reported that alkaloid reserpine and carbonylcyanide m-chlorophenylhydrazone (CCCP) can inhibit NorA multi-drug efflux. In order to explore theuniversality of drug efflux in microorganisms, 85 strains of Acinetobacter baumannii (A. baumannii)were tested using reserpine and CCCP. The quinolone-resistant-determining region (QRDR) of gyrA andparC genes in 35 isolates of A. baumannii were amplified by polymerase chain reaction (PCR) andsequenced by DNA sequencer. The correlation between resistant mutation regularity and bacterial drugefflux were analysed.

EFFECTS OF RESERPINE ON THE DEVELOPMENT OF NEUROPSYCHOGENIC HYPERTENSION IN DOGS

The effects of reserpine on the blood pressure, heart rate, higher nervous activity andplasma catecholamine level during the development of neuropsychogenic hypertension inducedby overstrain of the central nervous system have been studied in dogs. Overstrain (intensified tension) of the higher nervous activities was induced by a scheduleof irregularly arranged strengthening of the conditional stimuli with electric stimuli on theskin. After completion of three stimulative periods, 4 of the 5 untreated control and 2 ofthe 5 reserpine-treated dogs were found to have developed hypertension. The blood pressuremeasured in Chamber A (the room for blood pressure measurement) was much lower than thatmeasured in Chamber B, i.e. in the experimental environment. The results showed that reser-pine may have some inhibitory influence on the development of this model of neuropsycho-genic hypertension, yet it could not prevent its development completely.

利血平和丘脑下部促黄体素释放激素类似物(LHRH-A)对大鳞副泥鳅促性腺激素细胞的分泌活动和排卵的促进作用

利血平能使神经分泌细胞的儿茶酚胺贮存量减少甚至消耗殆尽,导致多巴胺作为GRIF的作用减弱,从而显著增强LHRH-A促进GtH分泌和诱导排卵的效应。对大鳞副泥鳅,利血平和LHRH-A同时注射或者利血平比LHRH-A提前3小时注射,都能激活GtH细胞,显著增强其分泌活动并诱导排卵。利血平的最低有效剂量为1—5微克/克体重。利血平(25微克/克体重)+LHRH-A(0.05微克/克体重)的催产效果和多巴胺拮抗物pimozide(1微克/克体重)+LHRH-A(0.05微克/克体重)的催产效果一样,排卵率都达到了100％。

Gastrin,somatostatin,and experimental disturbance of the gastrointestinal tract in rats

INTRODUCTIONThe field of gastrointestinal hormones has expanded at a dizzying rate[1-4].Gastrointestinal hormones as regulatory peptides that appear to be major components of bodily integration and have important regulatory actions on physioligical function of the gastrointestinal tract .The successful isolation of some gastrointestinal hormones and the development of sensitive methods for their detection have led to the unexpected finding that they also exist in the brain .

A Study on Antitoxic Role of Vesicular Monoamine Transporter 2 in Transgenic Chinese Hamster Overy Cells

Objective : To study the antitoxic role of vesicular monoamine transporter 2 (VMAT2) in transgenic Chinese Hamster ovary (CHO) cell. Methods :With the technology of trans-gene from PC 12 to CHO, MTT reduction assay was used to detect MPP+ toxic effect on wild type CHO (wtCHO) and transgenic CHO. Meanwhile, the role of reserpine was also observed in MPP+ toxic effects. Results :The sensitivity of transgenic CHO to MPP+ was much less than that of wtCHO with 0. 5 mmol/L MPP+. Transgenic CHO had the same sensitivity as wtCHO if rotenone was given. WtCHO, by given reserpine alone, didn't change its sensitivity to MPP+. Conclusions :VMAT2 has protective effect on transgenic CHO by transporting MPP+ to vesicles.

Effect of Shashen Maidong Decoction on Gastric Motility in vivo

Objective: To evaluate the effect of Shashen Maidong Decoction (SSMDD) on gastric motility.Method: Effect of SSMDD on the gastric motility of mice and rats was observed in vivo by administration of SSMDD in various dosages and observation on gastric phenol red excretion rate, gastric emptying rate, frequency and amplitude of contraction of fundic longitudinal muscles, etc. Results: SSMDD could reduce markedly the gastric phenol red excretion rate of mice, antagonize the acceleration of gastric emptying induced by neostigmine, inhibit the frequency and amplitude of contraction of fundic longitudinal muscle, slow down the frequency and decrease the amplitude of gastric peristalsis, and reduce the gastric hypermotility induced by indomethacin significantly. Conclusion: SSMDD has evident inhibition action on motility of experimental animals in vivo, its mechanism might be related with adrenergic nerve and metabolism of prostaglandin E.