<unk>  has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant properties. It is a high-potency and an benzodiazepine, and its uniqueness, advantages, and disadvantages are largely explained by its pharmacokinetic properties (poor water and lipid solubility, high protein binding and anoxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative potency<unk>  1 mg is equal in effect to diazepam 10 mg). The biological half-life of<unk>  is 10–20 hours. Pharmacokinetics<unk>  is highly protein bound and is extensively metabolized into pharmacologically inactive metabolites. Due to its poor lipid solubility,<unk>  is absorbed relatively slowly by mouth and is unsuitable for rectal administration. However, its poor lipid solubility and high degree of protein binding (85–90%) mean its volume of distribution is mainly the vascular compartment, causing relatively prolonged peak effects. This contrasts with the highly lipid-soluble diazepam, which, although rapidly absorbed orally or rectally, soon redistributes from the serum to other parts of the body, in particular, body fat. This explains why one<unk>  dose, despite its shorter serum half-life, has more prolonged peak effects than an equivalent diazepam dose.<unk>  is rapidly conjugated at its 3-hydroxy group into<unk>  glucuronide which is then excreted in the urine.<unk>  glucuronide has no demonstrable CNS activity in animals. The plasma levels of<unk>  are proportional to the dose given. There is no evidence of accumulation of<unk>  on administration up to six months. On regular administration, diazepam will accumulate, since it has a longer half-life and active metabolites, these metabolites also have long half-lives. Clinical example: Diazepam has long been a drug of choice for status epilepticus; its high lipid solubility means it gets absorbed with equal speed whether given orally, or rectally (nonintravenous routes are convenient in outside hospital settings), but diazepam's high lipid solubility also means it does not remain in the vascular space, but soon redistributes into other body tissues. So, it may be necessary to repeat diazepam doses to maintain peak anticonvulsant effects, resulting in excess body accumulation.<unk>  is a different case; its low lipid solubility makes it relatively slowly absorbed by any route other than intravenously, but once injected, it will not get significantly redistributed beyond the vascular space. Therefore,<unk> 's anticonvulsant effects are more durable, thus reducing the need for repeated doses. If a person is known to usually stop convulsing after only one or two diazepam doses, it may be preferable because sedative after effects will be less than if a single dose of<unk>  is given (diazepam anticonvulsant/sedative effects wear off after 15–30 minutes, but<unk>  effects last 12–24 hours). The prolonged sedation from<unk>  may, however, be an acceptable trade-off for its reliable duration of effects, particularly if the person needs to be transferred to another facility. Although<unk>  is not necessarily better than diazepam at initially terminating seizures,<unk>  is, nevertheless, replacing diazepam as the intravenous agent of choice in status epilepticus.<unk>  serum levels are proportional to the dose administered. Giving 2 mg oral<unk>  will result in a peak total serum level of around 20 ng/ml around two hours later, half of which is<unk> , half its inactive metabolite,<unk> -glucuronide. A similar<unk>  dose given intravenously will result in an earlier and higher peak serum level, with a higher relative proportion of unmetabolised (active)<unk> . On regular administration, maximum serum levels are attained after three days. Longer-term use, up to six months, does not result in further accumulation. On discontinuation,<unk>  serum levels become negligible after three days and undetectable after about a week.<unk>  is metabolized in the liver by conjugation into inactive<unk> -glucuronide. This metabolism does not involve liver oxidation, so is relatively unaffected by reduced liver function.<unk> -glucuronide is more water-soluble than its precursor, so gets more widely distributed in the body, leading to a longer half-life than<unk> .<unk> -glucuronide is eventually excreted by the kidneys, and, because of its tissue accumulation, it remains detectable, particularly in the urine, for substantially longer than<unk> . Pharmacodynamics Relative to other benzodiazepines,<unk>  is thought to have high affinity for GABA receptors, which may also explain its marked amnesic effects. Its main pharmacological effects are the enhancement of the effects of the neurotransmitter GABA at the GABAA receptor. Benzodiazepines, such as<unk> , enhance the effects of GABA at the GABAA receptor via increasing the frequency of opening of the chloride ion channel on the GABAA receptors; which results in the therapeutic actions of benzodiazepines. They, however, do not on their own activate the GABAA receptors, but require the neurotransmitter GABA to be present. Thus, the effect of benzodiazepines is to enhance the effects of the neurotransmitter GABA. The magnitude and duration of<unk>  effects are dose-related, meaning larger doses have stronger and longer-lasting effects, because the brain has spare benzodiazepine drug receptor capacity, with single, clinical doses leading only to an occupancy of some 3% of the available receptors. The anticonvulsant properties of<unk>  and other benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to get limited, by the benzodiazepine effect of slowing recovery of sodium channels from inactivation to deactivation in mouse spinal cord cell cultures, hence prolonging the refractory period.
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Triazolam
Nimetazepam
Nordazepam