Research and Clinical Trials on Clonazepam (Klonopin, Rivotril)

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This list of current clinical research trials on Clonazepam (Klonopin, Rivotril) is followed by a short set of abstracts from the most recent research articles published on the drug.

Clonazepam (Klonopin, Rivotril) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Clonazepam (Klonopin, Rivotril).

 

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Current Research Literature on Clonazepam (Klonopin, Rivotril)

Here are abstracts for some of the latest research articles to have appeared on Clonazepam (Klonopin, Rivotril):

Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice.

Methods Find Exp Clin Pharmacol. 2009 Sep; 31(7): 423-32
Akula KK, Dhir A, Kulkarni SK
The present study was undertaken to compare the anticonvulsant effect of various antiepileptic drugs on the intravenous pentylenetetrazol (PTZ)-induced seizure threshold in mice. Minimal doses of PTZ needed to induce different phases (myoclonic jerks, generalized clonus and tonic extensor) of convulsions were recorded as an index of seizure threshold. Furthermore, TID(50) (the dose of an anticonvulsant drug required to increase the PTZ seizure threshold for tonic extensor by 50%) was calculated for all drugs, and from these values the potency ratio was determined. Pentobarbital (10-40 mg/kg i.p.), phenobarbital (5-20 mg/kg i.p.), phenytoin (20-40 mg/kg i.p.), carbamazepine (5-20 mg/kg i.p.), diazepam (0.5-2 mg/kg i.p.), chlordiazepoxide (1-4 mg/kg i.p.), triazolam (0.02-0.08 mg/kg i.p.), clonazepam (0.03125-0.25 mg/kg i.p.), GABA (25-100 mg/kg i.p.), ethanol (1000-4000 mg/kg of 10% v/v p.o.), ashwagandha (50-200 mg/kg p.o.), tiagabine (20 and 40 mg/kg i.p.), gabapentin (50-200 mg/kg i.p.), pregabalin (10-40 mg/kg i.p.), progesterone (20-80 mg/kg s.c.), adenosine (25-200 mg/kg i.p.) and rofecoxib (1-4 mg/kg i.p.) exhibited dose-dependent anticonvulsant effects. The TID(50) of triazolam was found to be the lowest among all the drugs tested, indicating higher potency. The relative potency of standard drugs to increase the PTZ seizure threshold for tonic extensor was found to be: triazolam > clonazepam > diazepam > rofecoxib > chlordiazepoxide > phenobarbital > carbamazepine > pentobarbital > pregabalin > phenytoin > progesterone > tiagabine > GABA > adenosine > gabapentin > ashwagandha > ethanol. The results of the present study indicate that the intravenous PTZ seizure threshold may be useful for assessing the anticonvulsant effect of drugs effective against different stages of convulsions.

Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study.

Int Clin Psychopharmacol. 2009 Nov 5;
Papakostas GI, Clain A, Ameral VE, Baer L, Brintz C, Smith WT, Londborg PD, Glaudin V, Painter JR, Fava M
Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be both common and difficult to treat, with antidepressant monotherapy often yielding modest results. We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression. We conducted a post-hoc analysis of an existing dataset (N=80), from a 3-week, randomized, double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD. The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement. Anxious depression status was not found to predict symptom improvement, or serve as a moderator of clinical improvement to cotherapy versus monotherapy. However, the advantage in remission rates in favor of cotherapy versus monotherapy was, numerically, much larger for patients with anxious depression (32.2%) than it was for patients without anxious MDD (9.7%). The respective number needed to treat statistic for these two differences in response rates were, approximately, one in three for patients with anxious depression versus one in 10 for patients without anxious depression. The efficacy of fluoxetine-clonazepam cotherapy compared with fluoxetine monotherapy was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression.

Physico-Chemical Characterization and In Vitro Dissolution Assessment of Clonazepam-Cyclodextrins Inclusion Compounds.

AAPS PharmSciTech. 2009 Oct 29;
Patel R, Purohit N
The objectives of this research were to prepare and characterize inclusion complexes of clonazepam with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin and to study the effect of complexation on the dissolution rate of clonazepam, a water-insoluble lipid-lowering drug. The phase-solubility profiles with both cyclodextrins were classified as A(P)-type, indicating the formation of 2:1 stoichiometric inclusion complexes. Gibbs free energy [Formula: see text] values were all negative, indicating the spontaneous nature of clonazepam solubilization, and they decreased with increase in the cyclodextrins concentration, demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrins increased. Complexes of clonazepam were prepared with cyclodextrins by various methods such as kneading, coevaporation, and physical mixing. The complexes were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry studies. These studies indicated that complex prepared kneading and coevaporation methods showed successful inclusion of the clonazepam molecule into the cyclodextrins cavity. The complexation resulted in a marked improvement in the solubility and wettability of clonazepam. Among all the samples, complex prepared with hydroxypropyl-beta-cyclodextrin by kneading method showed highest improvement in in vitro dissolution rate of clonazepam. Mean dissolution time of clonazepam decreased significantly after preparation of complexes and physical mixture of clonazepam with cyclodextrins. Similarity factor indicated significant difference between the release profiles of clonazepam from complexes and physical mixture and from plain clonazepam. Tablets containing complexes prepared with cyclodextrins showed significant improvement in the release profile of clonazepam as compared to tablet containing clonazepam without cyclodextrins.

Allosteric modulation by benzodiazepines of GABA-gated chloride channels of an identified insect motor neurone.

Invert Neurosci. 2009 Oct 22;
Buckingham SD, Higashino Y, Sattelle DB
The actions of benzodiazepines were studied on the responses to GABA of the fast coxal depressor (D(f)) motor neurone of the cockroach, Periplaneta americana. Ro5-4864, diazepam and clonazepam were investigated. Responses to GABA receptors were enhanced by both Ro5-4864 and diazepam, whereas clonazepam, a potent-positive allosteric modulator of human GABA(A) receptors, was ineffective on the native insect GABA receptors of the D(f) motor neurone. Thus, clear pharmacological differences exist between insect and mammalian native GABA-gated chloride channels with respect to the actions of benzodiazepines. The results enhance our understanding of invertebrate GABA-gated chloride channels which have recently proved important in (a) comparative studies aimed at identifying human allosteric drug-binding sites and (b) understanding the actions of compounds used to control ectoparasites and insect crop pests.

Sleep-related breathing and sleep-wake disturbances in ischemic stroke.

Neurology. 2009 Oct 20; 73(16): 1313-22
Hermann DM, Bassetti CL
BACKGROUND: Sleep-related breathing disturbances (SDB) and sleep-wake disturbances (SWD) are often neglected in stroke patients. Recent studies suggest that they are frequent and have an impact on stroke outcome. METHODS: We review current knowledge about frequency, clinical presentation, and consequences of poststroke SDB and SWD, and discuss treatment options. RESULTS: SDB, presenting with obstructive, central, or mixed apneas, is present in 50%-70% of stroke patients. We recommend screening for SDB in all stroke patients by respirography. Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive SDB, which reverses the vascular risk of the patients. In the absence of controlled trials, CPAP treatment should be reserved for patients with severe obstructive SDB, daytime symptoms (e.g., sleepiness), or high cardiovascular risk profile. Oxygen and adaptive servoventilation may be used for central SDB. SWD including insomnia, disturbances of wakefulness (hypersomnia, excessive daytime sleepiness, fatigue), sleep-related movement disorders (restless legs syndrome, periodic limb movements during sleep), and parasomnias (REM sleep behavior disorder) are found in 10%-50% of patients. SWD are associated with cognitive disturbances and may compromise neurologic recovery. Hypnotics and sedative antidepressants may aggravate SDB and neurologic recovery and should be used with caution. For disturbances of wakefulness, dopaminergic drugs, modafinil, or activating antidepressants may be considered. Poststroke sleep-related movement disorders can be treated with dopaminergic drugs; REM sleep behavior disorder with clonazepam. CONCLUSIONS: Sleep-related breathing disturbances and sleep-wake disturbances are frequent conditions that affect stroke outcome. In view of existing treatment options, these conditions deserve the neurologist's awareness.

 

This page was last reviewed by Dr Greg Mulhauser, Monday, 1 June 2009.

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