Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new catapres research articles will be listed here shortly after becoming available to us.
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Medical research on catapres
Neuroscience. 2008 Sep 3;
Ortiz JP, Close LN, Heinricher MM, Selden NR
Stress-induced hypoalgesia (SIH) is an adaptive behavioral phenomenon mediated in part by the amygdala. Acute stress increases amygdalar noradrenaline levels and focal application of alpha(2)-adrenoceptor agonists in the central nucleus of the amygdala (CeA) is antinociceptive. We hypothesized that alpha(2)-adrenoceptor antagonist administration into the CeA may block SIH. Bilateral microinjections of drug or saline via chronically implanted CeA cannulae were followed by either a period of restraint stress or rest. The nocifensive paw-withdrawal latency (PWL) to a focused beam of light was measured. PWLs were longer in restrained rats, constituting SIH. Microinjection of the alpha(2)-adrenoceptor antagonist idazoxan into the CeA prior to restraint blocked SIH. Idazoxan administration in unrestrained rats had no effect. Microinjection of the alpha(2)-adrenoceptor agonist clonidine in unrestrained rats caused dose dependent hypoalgesia, mimicking the effects of environmental stress. alpha(2)-Adrenoceptor function in the CeA is necessary for restraint-induced SIH.
[Arterial hypertension - dosing recommendations at beginning and end of treatment.]
Ther Umsch. 2008 Oct; 65(10): 577-84
Middeke M
In the treatment of arterial hypertension different dosing strategies like slow dose escalation at the beginning of antihypertensive therapy and gradual dose taper or abrupt withdrawal of drugs may be appropriate. In general treatment should be initiated with a long acting drug at a low dose and doses should only slowly be increased under close blood pressure control. The dose-response curve usually is very flat, whilst adverse effects may rise disproportionately with higher doses. Therefore dose increases to maximal doses are no longer desirable in modern antihypertensive therapy and combinations of two drugs as fixed combinations at low doses should be preferred. Modern antihypertensive drugs can be abruptly and safely withdrawn in most patients. However, a gradual dose taper can be necessary in patients with coronary heart disease treated with cardioselective beta-blockers. Withdrawal is easier and safer under telemetric blood pressure control than self measured blood pressure. The same treatment approach applies to reserve medications like alpha-blockers, centrally acting drugs as clonidine, methyldopa, moxonidine, the vasodilators hydralazine and minoxidil, and other antihypertensives like reserpine and guanethidine. Withdrawal phenomena have to be considered in individual cases and particularly with clonidine after long-term use.
[Particularities of drug dosing at the beginning and end of therapy.]
Ther Umsch. 2008 Oct; 65(10): 573-5
Haefeli WE, Walter-Sack I
The starting dose of a drug determines both onset of action and tolerability of the compound. In contrast to most drug therapies, which may immediately be started with regular maintenance doses, compounds undergoing substantial autoinduction (e.g. carbamazepine) must be administered at slowly increasing doses to compensate for an initially low clearance and to avoid toxicity. Gradual dose escalation is also necessary whenever a drug induces substantial counter-regulatory reflex activation or adaptation processes. In these cases administration of standard doses may lead to excessive adverse reactions (e.g. cardiac decompensation after initiation of beta-receptor antagonism). Also in these situations cautious dose titration is required. After long-term administration those drugs should be withdrawn only very carefully to avoid potentially life-threatening withdrawal syndromes like hypertensive emergencies after abrupt discontinuation of clonidine or rebound epilepsies after discontinuation of anticonvulsants.
Am J Drug Alcohol Abuse. 2008; 34(5): 611-6
Yu E, Miotto K, Akerele E, O'Brien CP, Ling W, Kleber H, Fischman MW, Elkashef A, Herman BH, Al-Ghananeem AM
OBJECTIVES: The objective of this investigation was to characterize the pharmacokinetic profile of lofexidine. Lofexidine is an orally bioavailable alpha 2-adrenergic receptor agonist analogue of clonidine that acts centrally to suppress opiate withdrawal symptoms. METHODS: During the detoxification period of a phase 3 placebo-controlled, randomized, double-blind trial, six subjects were entered in this preliminary pharmacokinetic study. RESULTS: Pharmacokinetic analysis of plasma samples collected during study day 7 indicated that C(max) was 3242 +/- 917 ng/L. The mean trough levels between the study days were not significantly different (p > .05), suggesting that the subjects were at steady-state. CONCLUSIONS: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine clinical pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis.
Nootropic activity of tuber extract of Pueraria tuberosa (Roxb).
Indian J Exp Biol. 2008 Aug; 46(8): 591-8
Rao NV, Pujar B, Nimbal SK, Shantakumar SM, Satyanarayana S
Nootropic effect of alcoholic (ALE; 50, 75, 100 mg/kg) and aqueous (AQE; 100, 200, 400 mg/kg) extracts of P. tuberosa was evaluated by using Elevated Plus Maze (EPM), scopolamine-induced amnesia (SIA), diazepam-induced amnesia (DIA), clonidine-induced (NA-mediated) hypothermia (CIH), lithium-induced (5-HT mediated) head twitches (LIH) and haloperidol-induced (DA- mediated) catalepsy (HIC) models. Piracetam was used as the standard drug. A significant increase in inflexion ratio (IR) was recorded in EPM, SIA and DIA models. A significant reversal effect was observed on rectal temperature in CIH model, reduction of head twitches in LIH models. However no significant reduction in catalepsy scores in HIC models were observed with test extracts and standard piracetam. The results indicate that nootropic activity observed with ALE and AQE of tuber extracts of P. tuberosa could be through improved learning and memory either by augmenting the noradrenaline (NA) transmission or by interfering with 5-hydroxytryptamine (5-HT) release. Further, the extracts neither facilitated nor blocked release of the dopamine (DA). Thus ALE and AQE elicited significant nootropic effect in mice and rats by interacting with cholinergic, GABAnergic, adrenergic and serotonergic systems. Phytoconstituents like flavonoids have been reported for their nootropic effect and these are present in both ALE and AQE extracts of tubers of P. tuberosa (Roxb) and these active principles may be responsible for nootropic activity.
[High-dose methadone detoxification in a hospital unit. Clinical experience]
Adicciones. 2008; 20(3): 245-9
Ochoa E, Salvador E, Madoz-Gúrpide A, Lázaro M
The increase in opiate addicts in treatment with methadone, coupled with improved survival of HIV patients, has meant an increase in the demand for detoxification from this substance in our environment. It is common practice in hospital detoxification units to request a maximum dose of methadone (around 40 mg) on beginning detoxification treatment. However this is not always possible, due to the time needed for a gradual decrease for outpatients making daily visits to the methadone dispensing centres, due to the appearance of withdrawal symptoms, or because the patient starts out from very high doses of methadone. Reported here is an experience with 22 inpatients who over the last two years underwent detoxification from methadone without requesting from their treatment centres a maximum-limit dose at the start of their treatment. During the detoxification they are given treatment with clonidine and benzodiazepines (dosage being adjusted according to concomitant use of alcohol, benzodiazepines and cocaine) and non-opiate-based painkillers. On the seventh day they are given 50 mg of naltrexone. Of these addicts, 21 completed the detoxification adequately.
Paediatr Anaesth. 2008 Oct; 18(10): 1000-1
Aouad MT, Moukaddem FH, Akel SR, Kanazi GE
Acta Anaesthesiol Taiwan. 2008 Sep; 46(3): 118-23
Lai YC, Tsai PS, Huang CJ
Background: We sought to evaluate the effects of clonidine on type-2 cationic amino acid transporter (CAT-2) transcription in endotoxin-activated murine macrophages. Methods: To determine the effects of clonidine on CAT-2 transcription, confluent murine macrophages (RAW264.7 cells) were treated with 1x phosphate buffered saline, clonidine (1000 muM), lipopolysaccharide (LPS, 100 ng/mL), or LPS plus clonidine (10, 100, or 1000 muM). After reacting with LPS for 18 hours or a comparable duration in groups without LPS, cell cultures were harvested and the CAT-2 mRNA concentration was assayed. To determine the stability of CAT-2 mRNA, confluent macrophages were treated with LPS or LPS plus clonidine (100 muM). After reacting with LPS for 6 hours, CAT-2 transcription was terminated and the stability of CAT-2 mRNA was determined. Results: The CAT-2 mRNA concentration of cell cultures receiving LPS plus clonidine (100 muM) or LPS plus clonidine (1000 muM) were significantly higher than that of the cell cultures receiving LPS alone, whereas the CAT-2 mRNA concentrations of cell cultures receiving LPS plus clonidine (10 muM) was comparable to that of cell cultures receiving LPS alone. The data indicated that clonidine significantly enhanced LPS-induced CAT-2 transcription. The estimated half-life of CAT-2 mRNA of cell cultures receiving LPS was similar to that of cell cultures receiving LPS plus clonidine. These results indicated that clonidine did not affect CAT-2 mRNA stability. Conclusion: Clonidine enhances CAT-2 transcription in endotoxin-activated murine macrophages.
Pulsed radiofrequency treatment of lower extremity phantom limb pain.
Clin J Pain. 2008 Oct; 24(8): 736-9
Wilkes D, Ganceres N, Solanki D, Hayes M
BACKGROUND: Phantom limb pain can be challenging to treat. We present a patient who developed severe phantom limb pain after revision of her lower extremity amputation due to the continued progression of peripheral vascular disease. Multiple treatment modalities had been tried without success. Pulsed radiofrequency has been successfully used to manage a number of pain syndromes. OBJECTIVE: The present case report describes the use of pulsed radiofrequency treatment for phantom limb pain. METHODS: The authors initially preformed regional blocks of femoral and sciatic nerve with 0.375% bupivicaine 15 cc and 50 microg clonidine to control the patient's pain. The blocks provided good pain relief but with limited duration. Based on reports of prolonged pain relief provided by pulsed radiofrequency treatment for other chronic pain conditions such as lumbrosacral spondylosis, we decided to apply this treatment to the patient's sciatic nerve. The patient underwent pulsed radiofrequency treatment with 2 cycles of 120 seconds at 42 degrees, pulse rate of 2 pulse/second, and pulse duration of 20 milliseconds. RESULTS: Our report shows that the sciatic nerve block with bupivicaine and clonidine, initiated approximately 3 years after amputation, produced modest short-term relief. The pulsed radiofrequency treatment resulted in long-term relief of phantom limb pain. The patient was able to wean herself off all oral medications and has been pain free for 4 months.
Drug Alcohol Depend. 2008 Sep 19;
Ziedonis DM, Amass L, Steinberg M, Woody G, Krejci J, Annon JJ, Cohen AJ, Waite-O'Brien N, Stine SM, McCarty D, Reid MS, Brown LS, Maslansky R, Winhusen T, Babcock D, Brigham G, Muir J, Orr D, Buchan BJ, Horton T, Ling W
Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes.