Clonidine

Effect of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna speciosa), on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 nM - 3 μM) inhibited the ileum contraction elicited by electrical stimulation, and its pD2 value was 6.91 ± 0.04 (n = 5). Morphine (1 nM − 1 μM) also inhibited the electrically stimulated contraction in a concentration-dependent manner (pD2 7.68 ± 0.11; n = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3–10 μM) did not show any effect on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10–300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of concentration-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA2) in the presence of mitragynine or morphine. Mitragynine (3–10 μM) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 μM) and atropine (1 μM) inhibited the withdrawal contraction. The present results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor.

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS wa...

Purpose This review on ultrarapid detoxification examines the pharmacology, techniques, and efficacy of this potentially promising technique and contrasts it with conventional treatment modalities. Source The information found here is derived from experiences at the Texas Tech University, government reports, and peer reviewed journals. Principal findings Incidence and prevalence of heroin use is on the rise. Social and treatment costs suggest that this problem is staggering. Approximately 400,000 patients are enrolled in or are actively seeking methadone therapy. While many of these individuals want to undergo detoxification, traditional techniques, including methadone tapering are usually unsuccessful. The withdrawal syndrome is extremely unpleasant, may be fatal, and deters patients from completing the detoxification process. Ultrarapid detoxification entails general anesthesia in conjunction with large boluses of narcotic antagonists. This combination allows the individual to com...

Clonidine disrupts the NREM/REM sleep cycle and reduces the incidence of rhythmic masticatory muscle activity (RMMA) characteristic of sleep bruxism (SB). RMMA/SB is associated with brief and transient sleep arousals. This study investigates the effect of clonidine on the cyclic alternating pattern (CAP) in order to explore the role of cyclic arousal fluctuation in RMMA/SB. Polysomnographic recordings from a pharmacological study. University sleep research laboratory. Sixteen SB subjects received a single dose of clonidine or placebo at bedtime in a crossover design. Sleep variables and RMMA/SB index were evaluated. CAP was scored to assess arousal instability between sleep-maintaining processes (phase A1) and stronger arousal processes (phases A2 and A3). Paired t-tests, ANOVAs, and cross-correlations were performed. Under clonidine, CAP time, and particularly the number of A3 phases, increased (P≤0.01). RMMA/SB onset was time correlated with phases A2 and A3 for both placebo and c...

According to the Substance Abuse and Mental Health Services Administration (SAMHSA, 2016), within the past year 21.5 million individuals over the age of 12 suffer from addiction to various substances in America. The most commonly categorized substances, in their respective order of frequency of use, are as follows: alcohol, tobacco, cannabis, stimulants, hallucinogens, and opioids. Medical professionals attempting to effectively treat clients who suffer from either single or co-morbid substance abuse addiction may incorporate psychopharmacological aids in treatment. Anti-depressants, benzodiazepine, naltrexone, and methadone are just a few of the wide array of aids chosen as tools to assist addicts with ways to cope with drug withdrawal and detox as well as alcohol withdrawal and detox. Additionally, these psychopharmacological treatments assist the user in overcoming addiction. Despite their prevalence in substance abuse treatment, their incorporation into an individual’s treatment should be made on a case-by-case basis as each individual aid emanates its own unique set of strengths and weaknesses. This paper intends to elucidate a few popular, or widely implemented, psychopharmacological aids used in such treatments based on intended purpose, effectiveness, and supporting research. For the purpose of conciseness, a few will be evaluated within the parameters of drug withdrawal and detox, alcohol addiction, and heroin and opiate addiction. This paper should constrain the reader to seek further analysis of variant and covariant research on the wide array of alternative psychopharmacological aids and their intended uses.

sialorrhea is one of the common nonmotor, non-neuropsychiatric symptoms in Parkinson's disease and its pre-sence can cause limitation in the patient's social life. The traditional treatment with anticholinergic medication is capable of triggering important neuropsychiatric complications. this is a prospective, double-blind, placebo compared study, which follow-up Parkinson's disease patients for 3 months. we measured the efficacy of clonidine in the management of sialorrhea. The study was performed in 32 patients (20 males and 12 females), with a mean age of 70.75 years and mean duration of the disease of 8.84 years. Randomly, 17 patients received clonidine 0.15 mg/day and the remaining 15 patients received placebo. Both groups were made up of subjects with similar characteristics, age, years of illness, sex, stage of disease (H and Y), disability (S and C) and motor score (UPDRS). Likewise, salivation affected both groups in the same intensity. We used the variable anal...

Smoking is related to 30% of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS), enhances alertness and reduces the appetite. A 50% reduction of nicotine consumption may trigger withdrawal symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy) and second-line (clonidine and nortriptyline) drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinen...

This study was conducted to assess the effects of various excipients in 10 different Tizanidine hydrochloride tablet dosage forms that were prepared by direct compression method (DC). Various excipients are available for DC method; we selected those excipients that are used commonly in tablet manufacturing. The excipients used included lactose anhydrous, di-basic calcium phosphate anhydrous, starch, talc, sodium carboxy methyl cellulose, polyvinyl pyrrolidone (PVP), silicon dioxide (Aerosil), stearic acid, magnesium stearate and microcrystalline cellulose (Avicel). These tablets were then evaluated by performing different pharmacopoeial and non-pharmacopoeial tests (i.e. diameter, hardness, thickness, weight variation, disintegration and assay). It was observed that Formulations B, D and H of Tizanidine hydrochloride gave best results within USP specified limits for the tests employed among all the formulations whereas Formulations F and G showed poor friability, disintegration and ...

To compare the efficacy of clonidine vs propranolol in the control of essential tremor, a double-blind randomized controlled trial with a one year follow-up was designed to obtain 80 % power and 95 % confidence level. The participants (186 patients with the essential tremor diagnosis) were recruited from the community, 122 (65.6 %) of these patients completed the trial. They were assessed using a Clinical-Evaluation Scale for Tremor and were examined 5 times, once at baseline and 4 times during the treatment phase. We used ANOVA with Bonferroni corrections, a p> value of 0.01 was considered significant. Dropouts due to side effects were compared using the Fisher's exact X (2) test for two tails, a p>value of 0.05 was considered statistically significant. Propranolol as well as clonidine (p> = 0.005) proved to be statistically efficacious (p> = 0.0005). Propranolol was not more efficacious than clonidine (p> = 0.4). Dropouts were significantly higher in the clonidi...

International chronic obstructive pulmonary disease guidelines recommend that smokers be strongly advised to quit, and should be offered help in doing so. The most effective smoking-cessation interventions combine behavioural support with pharmacotherapies. For smokers who do not wish to use nicotine replacement treatments, bupropion is a safe and effective non-nicotine alternative first-line treatment. Nortriptyline and clonidine have demonstrated efficacy in aiding smoking cessation, but are regarded as second-line therapies. A number of other non-nicotine treatments show promise, but more data are required before these can be recommended in assisting smokers to stop.

Clonidine, a specific alpha-2-adrenergic receptor agonist, has been suggested to improve symptoms of gastroparesis in diabetics with diarrhoea. The aim of this study was to investigate the effects of clonidine on gastric emptying and symptoms suggestive of gastroparesis in patients with longstanding diabetes mellitus and evidence of autonomic neuropathy. Six diabetics with chronic, refractory symptoms of bloating, nausea and vomiting were studied. Gastric emptying of a liquid nutrient meal (250 mL; 430 kcal) was evaluated by scintigraphy and symptoms were scored. Patients were treated with clonidine (median dose: 0.3 mg/day) for 2-12 weeks (median: 4 weeks), after which symptoms and gastric emptying were re-evaluated. Treatment was then sustained for a median follow-up period of 7 weeks (range: 2-56 weeks). Gastric emptying half-time values in diabetic patients ranged from 16 to 180 min (median: 100 min) and four patients had abnormally delayed emptying before treatment. In all patients, half-time values decreased during treatment (median: 35 min; range: 14-106 min, P < 0.025 vs. pre-treatment values) and in three of the four patients with abnormal gastric retention, half-time values returned to the normal range. During clonidine treatment, a substantial decrease in the score for symptoms was observed (median and range: 7.5; 2-9 vs. 0; 0-9). In four patients, symptoms virtually disappeared, an effect that was maintained throughout follow-up (6-56 weeks). These findings suggest that impairment of adrenergic influences on gastrointestinal motility control may play a role in the pathophysiology of diabetic gastroparesis and that clonidine may be a useful alternative for treating patients with this condition.

This article reviews current evidence for the efficacy of adding novel analgesic adjuncts to brachial plexus block, the goal of which is to prolong analgesic effect without the disadvantage of systemic side effects or prolonged motor block. It may also allow for a reduction in the total dose of local anesthetic used. Novel adjuncts studied to date include opioids, clonidine, neostigmine, and tramadol. Twenty-four studies were reviewed and assessed by using specific inclusion criteria, and only those studies satisfying these criteria were included in the final assessment. Satisfactory studies were then assessed for inclusion of a systemic control group to determine peripheral effect, as opposed to possible systemic effect, of an adjunct administered peripherally. Evidence regarding the analgesic benefit of opioid adjuncts remains equivocal and more evidence is required before their routine use can be recommended. Clonidine appears to have significant analgesic benefit and to cause minimal adverse effects when used in doses up to 150 microg. Data regarding other drugs, such as tramadol and neostigmine, are not sufficient to allow for any recommendations, and further studies are required.

Timolol was the first β blocker to be used as an anti-glaucoma agent and to date remains as the standard because none of the newer β blockers were found to be more effective. The high performance thin layer chromatographic method of analysis of timolol maleate is reported. The mobile phase selected was ethyl acetate–methanol–isopropyl alcohol–ammonia (25%) (80:20:2:1, v/v/v/v). The calibration curve of the drug was linear in the range of 100–600 ng. The spectrodensitometric analysis was carried out at 294 nm. The mean (±RSD) values of slope, correlation coefficient and intercept were 2487.5 (±0.9), 0.996 (±0.081) and 90463 (±1.1), respectively. The system precision and the method precision were excellent with an RSD of 2.8 and 1.004, respectively. The limits of detection and quantitation were 10 and 40 ng, respectively. The mean percent recovery was found to be 98.6. Timolol maleate was degraded by exposing the drug to heat, acid and base. The degraded products were found to be well separated from the pure drug with significantly different Rf values suggesting a stability indicating analysis method for quantification of timolol maleate in pharmaceutical preparations and as bulk drug. The method was utilized to analyze timolol maleate from conventional eye drops and novel sustained release solid polymeric ocular inserts and oral preparations. The reported method is simple, selective, precise, accurate, time saving and economic as compared to reported HPLC methods.

ABSTRACT Background Traffic safety is compromised whenever people participate in traffic under the influence of psychoactive substances, i.e. alcohol and prescription-and non-prescription drugs 1 . Crash rates have been shown to be higher in drivers under the influence of alcohol and prescription-and non-prescription drugs 2 . The incidence of drivers under the influence of psychoactive drugs in actual traffic is considerable (5-17%) and increasing in most western countries 3 . Epidemiological data of high quality on the use of illicit substances such as cannabis, MDMA, amphetamines and other psychostimulants in traffic are sparse, but seem to point out that driving home after a party under the influence of so-called 'party drugs' or 'dance drugs' is increasing. When interviewed at the location of a dance party in the Netherlands, 6% of those who indicated they would be driving home afterwards had used MDMA and was still under the influence 4 . Most likely this is an underestimation and usually this would occur during late night hours when accident statistics are already elevated. Several fatal and non-fatal injurious road-accidents have been reported in which MDMA was found in the plasma of drivers, or those held responsible for the crashes 5 . Eleven cases of crashes by 5 drivers 4-6 hours after MDMA use, i.e. when leaving dance-parties, have been described in somewhat more detail. Vehicle operation after MDMA use was manifested as bizarre behaviour, inadequate attention, alienation, speeding and increased risk taking 6 . These findings clearly stress the need to further investigate the putative impairing influence of illicit drugs on driving performance or driving-related psychomotor performance in an experimental manner 7 . Another issue, related to the above, is polydrug use in traffic. The incidence of concomitant use of other recreational drugs such as cannabis and alcohol among XTC users has been shown to be as high as 80-90% 8 . It has become increasingly clear that the effects of many drugs, when taken concurrently are not necessarily predictable on the basis of knowledge of their effects when given alone. When MDMA users take several drugs concurrently, they face the problem of knowing whether a specific combination of drugs causes an interaction. A drug interaction refers to the possibility that one drug may alter the intensity of pharmacological effects of another drug given concurrently. The net results may be enhanced or diminished effects of one or both drugs or the appearance of a new effect that has not been observed with either drug alone.