Oxcarbazepine structure activity relationship of diazepam

Oxcarbazepine - Wikipedia

For topiramate, felbamate, retigabine, losigamone and stiripentol, GABAAR . are sensitive to diazepam but not to zolpidem and are termed BZ-3 receptors. of benzodiazepine receptors and in the structure-activity relationships of their. Diazepam and other drugs in the benzodiazepine class are positive allosteric . including anticonvulsant and mood stabilizer carbamazepine and . Nevertheless, structure–activity relationship studies reveal modest. chemical similarities between carbamazepine, phenytoin and diazepam are pointed out. The kinetic No structure activity relation has so far been found in.

However, they should not usually be given for longer than 2—4 weeks. Although they are second-line agents, benzodiazepines can be used for a limited time to relieve severe anxiety and agitation. CPA guidelines note that after 4—6 weeks the effect of benzodiazepines may decrease to the level of placebo, and that benzodiazepines are less effective than antidepressants in alleviating ruminative worrythe core symptom of GAD.

However, in some cases, a prolonged treatment with benzodiazepines as the add-on to an antidepressant may be justified. Their use beyond 2 to 4 weeks is not recommended due to the risk of dependence.

The Committee on Safety of Medicines report recommended that where long-term use of benzodiazepines for insomnia is indicated then treatment should be intermittent wherever possible. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging the sleep time, and, in general, reducing wakefulness.

Other drawbacks of hypnotics, including benzodiazepines, are possible tolerance to their effects, rebound insomniaand reduced slow-wave sleep and a withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation. The efficacy of these two groups of medications is similar.

NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines.

Oxcarbazepine | C15H12N2O2 - PubChem

There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing the hypnotic based on cost and the patient's preference. In a hospital environment, intravenous clonazepamlorazepamand diazepam are first-line choices.

In the community, intravenous administration is not practical and so rectal diazepam or buccal midazolam are used, with a preference for midazolam as its administration is easier and more socially acceptable. However, drowsiness and tolerance become problems with continued use and none are now considered first-line choices for long-term epilepsy therapy.

In the UK, both clobazam and clonazepam are second-line choices for treating many forms of epilepsy. Therefore, the dose is slowly tapered over a period of up to six months or longer. Both are used in the detoxification of individuals who are motivated to stop drinking, and are prescribed for a short period of time to reduce the risks of developing tolerance and dependence to the benzodiazepine medication itself.

On the other hand, short-acting benzodiazepines may lead to breakthrough seizuresand are, therefore, not recommended for detoxification in an outpatient setting. Oxazepam and lorazepam are often used in patients at risk of drug accumulation, in particular, the elderly and those with cirrhosisbecause they are metabolized differently from other benzodiazepines, through conjugation.


Compared to other pharmacological treatments, benzodiazepines are twice as likely to lead to a relapse of the underlying condition upon discontinuation. Psychological therapies and other pharmacological therapies are recommended for the long-term treatment of generalized anxiety disorder. Antidepressants have higher remission rates and are, in general, safe and effective in the short and long term.

They can sedate patients receiving mechanical ventilation or those in extreme distress. Caution is exercised in this situation due to the risk of respiratory depressionand it is recommended that benzodiazepine overdose treatment facilities should be available. They also produce amnesiawhich can be useful, as patients may not remember unpleasantness from the procedure.

Diazepam and lorazepam are sometimes used. Lorazepam has particularly marked amnesic properties that may make it more effective when amnesia is the desired effect. Tizanidine has been found to have superior tolerability compared to diazepam and baclofen. Lorazepam is most commonly used but clonazepam is sometimes prescribed for acute psychosis or mania; [64] their long-term use is not recommended due to risks of dependence. Effectiveness was, however, found in one small study.

For that reason, they are contraindicated in people with myasthenia gravissleep apneabronchitisand COPD. Effects of benzodiazepines on newborns In the United States, the Food and Drug Administration has categorized benzodiazepines into either category D or X meaning potential for harm in the unborn has been demonstrated. Their use by expectant mothers shortly before the delivery may result in a floppy infant syndromewith the newborns suffering from hypotoniahypothermialethargyand breathing and feeding difficulties.

This syndrome may be hard to recognize, as it starts several days after delivery, for example, as late as 21 days for chlordiazepoxide. The symptoms include tremorshypertoniahyperreflexiahyperactivityand vomiting and may last for up to three to six months.

If used in pregnancy, those benzodiazepines with a better and longer safety record, such as diazepam or chlordiazepoxideare recommended over potentially more harmful benzodiazepines, such as temazepam [82] or triazolam. Using the lowest effective dose for the shortest period of time minimizes the risks to the unborn child.

Oxcarbazepine - Wikipedia

This may play a role in explaining diazepam's anticonvulsant properties. Binding of benzodiazepines to this receptor complex promotes binding of GABA, which in turn increases the total conduction of chloride ions across the neuronal cell membrane.

This increased chloride ion influx hyperpolarizes the neuron's membrane potential. As a result, the difference between resting potential and threshold potential is increased and firing is less likely. As a result, the arousal of the cortical and limbic systems in the central nervous system is reduced. Benzodiazepine drugs including diazepam increase the inhibitory processes in the cerebral cortex. Sustained repetitive firing seems limited by benzodiazepines' effect of slowing recovery of sodium channels from inactivation.

The onset of action is one to five minutes for IV administration and 15—30 minutes for IM administration. The duration of diazepam's peak pharmacological effects is 15 minutes to one hour for both routes of administration.

The half-life of diazepam in general is 30—56 hours. The distribution half-life of diazepam is two to 13 minutes. It easily crosses both the blood—brain barrier and the placentaand is excreted into breast milk. After absorption, diazepam is redistributed into muscle and adipose tissue. Continual daily doses of diazepam quickly build to a high concentration in the body mainly in adipose tissuefar in excess of the actual dose for any given day.

Absorption by any administered route and the risk of accumulation is significantly increased in the neonateand withdrawal of diazepam during pregnancy and breast feeding is clinically justified. It has several pharmacologically active metabolites. The main active metabolite of diazepam is desmethyldiazepam also known as nordazepam or nordiazepam. Its other active metabolites include the minor active metabolites temazepam and oxazepam. These metabolites are conjugated with glucuronide, and are excreted primarily in the urine.

Because of these active metabolites, the serum values of diazepam alone are not useful in predicting the effects of the drug. Diazepam has a biphasic half-life of about one to three days, and two to seven days for the active metabolite desmethyldiazepam. It is odorless, and has a slightly bitter taste. The British Pharmacopoeia lists it as being very slightly soluble in water, soluble in alcohol, and freely soluble in chloroform.

The United States Pharmacopoeia lists diazepam as soluble 1 in 16 ethyl alcohol, 1 in 2 of chloroform, 1 in 39 etherand practically insoluble in water. The pH of diazepam is neutral i. The solution for parenteral injection should be protected from light and kept from freezing.