5 mg Valium Roche packaging Australia<unk>  is a long-acting "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, clonazepam, lorazepam, oxazepam, nitrazepam, temazepam, flurazepam, bromazepam, and clorazepate.<unk>  has anticonvulsant properties. Benzodiazepines act via micromolar benzodiazepine binding sites as calcium channel blockers and significantly inhibit depolarization-sensitive calcium uptake in rat nerve cell preparations.<unk>  inhibits acetylcholine release in mouse hippocampal synaptosomes. This has been found by measuring sodium-dependent high-affinity choline uptake in mouse brain cells in vitro, after pretreatment of the mice with<unk>  in vivo. This may play a role in explaining<unk> 's anticonvulsant properties.<unk>  binds with high affinity to glial cells in animal cell cultures.<unk>  at high doses has been found to decrease histamine turnover in mouse brain via<unk> 's action at the benzodiazepine-GABA receptor complex.<unk>  also decreases prolactin release in rats. Mechanism of action Benzodiazepines are positive allosteric modulators of the GABA type A receptors (GABAA). The GABAA receptors are ligand-gated chloride-selective ion channels that are activated by GABA, the major inhibitory neurotransmitter in the brain. Binding of benzodiazepines to this receptor complex promotes the 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. The GABAA receptor is a heteromer composed of five subunits, the most common ones being two αs, two βs, and one γ (α2β2γ). For each subunit, many subtypes exist (α1–6, β1–3, and γ1–3). GABAA receptors containing the α1 subunit mediate the sedative, the anterograde amnesic, and partly the anticonvulsive effects of<unk> . GABAA receptors containing α2 mediate the anxiolytic actions and to a large degree the myorelaxant effects. GABAA receptors containing α3 and α5 also contribute to benzodiazepines myorelaxant actions, whereas GABAA receptors comprising the α5 subunit were shown to modulate the temporal and spatial memory effects of benzodiazepines.<unk>  is not the only drug to target these GABAA receptors. Drugs such as flumazenil also bind to GABAA to induce their effects.<unk>  appears to act on areas of the limbic system, thalamus, and hypothalamus, inducing anxiolytic effects. Benzodiazepine drugs including<unk>  increase the inhibitory processes in the cerebral cortex. 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 limited by benzodiazepines' effect of slowing recovery of sodium channels from inactivation. The muscle relaxant properties of<unk>  are produced via inhibition of polysynaptic pathways in the spinal cord. Pharmacokinetics<unk>  can be administered orally, intravenously (must be diluted, as it is painful and damaging to veins), intramuscularly (IM), or as a suppository. The onset of action is one to five minutes for IV administration and 15–30 minutes for IM administration. The duration of<unk> 's peak pharmacological effects is 15 minutes to one hour for both routes of administration. The half-life of<unk>  in general is 30–56 hours. Peak plasma levels occur between 30 and 90 minutes after oral administration and between 30 and 60 minutes after intramuscular administration; after rectal administration, peak plasma levels occur after 10 to 45 minutes.<unk>  is highly protein-bound, with 96 to 99% of the absorbed drug being protein-bound. The distribution half-life of<unk>  is two to 13 minutes.<unk>  is highly lipid-soluble, and is widely distributed throughout the body after administration. It easily crosses both the blood–brain barrier and the placenta, and is excreted into breast milk. After absorption,<unk>  is redistributed into muscle and adipose tissue. Continual daily doses of<unk>  quickly build to a high concentration in the body (mainly in adipose tissue), far in excess of the actual dose for any given day.<unk>  is stored preferentially in some organs, including the heart. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate, and withdrawal of<unk>  during pregnancy and breast feeding is clinically justified.<unk>  undergoes oxidative metabolism by demethylation (CYP 2C9, 2C19, 2B6, 3A4, and 3A5), hydroxylation (CYP 3A4 and 2C19) and glucuronidation in the liver as part of the cytochrome P450 enzyme system. It has several pharmacologically active metabolites. The main active metabolite of<unk>  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<unk>  alone are not useful in predicting the effects of the drug.<unk>  has a biphasic half-life of about one to three days, and two to seven days for the active metabolite desmethyldiazepam. Most of the drug is metabolised; very little<unk>  is excreted unchanged. The elimination half-life of<unk>  and also the active metabolite desmethyldiazepam increases significantly in the elderly, which may result in prolonged action, as well as accumulation of the drug during repeated administration.
Diazepam
Adinazolam
Ketazolam
Halazepam
Midazolam
Triazolam
Thiazepine
Quazepam