Subjective effects include anxiety suppression and sedation. The onset of diazepam’s action is faster than other benzodiazepines. It is however generally thought to have fewer recreational effects than other benzodiazepines such as clonazepam, Klonopin, and alprazolam, (Xanax).
The toxicity of Diazepam has been considered low. It is possible to abuse it and can cause psychological and physical dependence if used for long periods. It can also cause respiratory depression and death if it is combined with alcohol, opioids, or other depressants. If you are using this substance, it is strongly recommended that harm reduction techniques be used.
For people who have used benzodiazepines for a long time, it is possible to be seriously ill or even die from abrupt withdrawal. It is recommended that one taper his or her dose, rather than abruptly stop.
It was found in many animal and plant species, and it is believed to be natural.
After chlordiazepoxide, (Librium) was approved in 1960, diazepam became the second benzodiazepine that Leo Sternbach from pharmaceutical company Hoffman-La Roche invented. Diazepam was released in 1963 as an improved version of Librium. It quickly became a hugely popular drug and quickly surpassed it in terms of sales. This helped Roche become a major in the pharmaceutical industry. Other pharmaceutical companies soon began to offer other benzodiazepine derivatives after this initial success.
Medical professionals have been recommending benzodiazepines as an alternative to barbiturates. They have a narrow therapeutic index and are less sedative at therapeutic doses. The dangers of diazepam overdose are far lower than those of barbiturates. Although initially supported by the public, diazepam and other benzodiazepine drugs like it was, there has been growing criticism of their use and calls for restrictions.
Roche promoted diazepam using an advertisement campaign created by the William Douglas McAdams Agency, under the direction of Arthur Sackler. It was the most popular pharmaceutical in America from 1969 to 1982. The peak annual sales of Valium tablets in 1978 were 2.3 billion. Although psychiatrists still prescribe diazepam to relieve anxiety for the short-term, neurology is now prescribing diazepam as a palliative treatment for certain types of epilepsy or spastic activity.
Diazepam belongs to the benzodiazepine drug class. Benzodiazepine drugs have a benzene ring fused with a diazepine ring. This is a seven-membered ring that has the two nitrogen constituents R1 and R4. Diazepam can be substituted for the methyl group at R1. The benzodiazepine rings are also bonded to aromatic phenyl rings at R5. A chlorine group is added to the benzyl rings of the bicyclic core. To form ketones, diazepam contains an oxygen group that is double-bonded to R2 in its diazepine rings. This oxygen substitution at R2 can be found in other benzodiazepine drugs that have the suffix –azepam.
Diazepam can be described as a 1,4-benzodiazepine. Diazepam is a solid white or yellow crystal with a melting temperature of 131.5 to 13.5 degC. It has a slightly bitter taste and is odorless. The pH of diazepam (i.e. pH = 7) is neutral. Additives such as benzoic acid/benzoate are used in injectable forms. Because diazepam is absorbed into plastics, liquid preparations should be stored in glass bottles and syringes. It can also leach into intravenous infusion tubing and plastic bags. The temperature, concentration, flow rate, and length of the tube all play a role in how much absorption occurs. If a precipitate has formed and is not dissolved, you should not administer Diazepam.
Diazepam is a long-acting “classical” benzodiazepine. Benzodiazepines act via micromolar benzodiazepine binding sites as calcium channel blockers and significantly inhibit depolarization-sensitive calcium uptake in rat nerve cell preparations. The release of acetylcholine in hippocampal synaptosomes from mice is inhibited by diazepam. This was confirmed by in vitro measurement of sodium-dependent high-affinity choline uptake in mouse brain cell cells after diazepam pretreatment in vivo. This could explain diazepam’s anticonvulsant qualities.
Benzodiazepines act as positive allosteric modators of GABA type A receptors (GABAA). GABAA receptors, which are ligand-gated ion channels that selectively bind to chloride ions, are activated in the brain by GABA. The binding of benzodiazepines and this receptor complex promotes GABA binding, which increases the total conduction of chloride ions across neuronal cell membranes. The neuron’s membrane potential is hyperpolarized by the increased chloride ion inflow. This increases the difference between resting and threshold potential, which makes firing less likely. This results in a decrease in the activity of the limbic and cortical systems within the central nervous system.
GABAA receptor heteromer is composed of five subunits. The most common are two as, two bis and one g (a2b2g). There are many subtypes for each subunit (a1-6 to b1-3 and g1-3). GABAA receptors that contain the a1 subunit mediate sedative, anterograde amnesic, and partially the anticonvulsive effects. GABAA receptors with a2 mediate anxiolytic and, in a large part, myorelaxant actions. GABAA receptors that contain a3 or a5 contribute to the myorelaxant effects of benzodiazepines. However, GABAA receptors that include the a5 subunit have been shown to modulate spatial and temporal memory effects of benzodiazepines.
Diazepam isn’t the only drug that targets these GABAA receptors. Flumazenil and other drugs can also be bound to GABAA in order to produce their effects. Anxiolytic effects are induced by diazepam, which appears to be acting on the limbic system and hypothalamus. Benzodiazepine drugs, including diazepam, increase inhibitory processes within the cerebral cortex.
The benzodiazepines have a wide range of effects. They bind to the benzodiazepine-receptor site and increase the effectiveness and effects of neurotransmitter Gamma-aminobutyric Acid (GABA) through their receptors. This site is the most important inhibitory receptor in the brain and modulates the effects of diazepam (or calming) on the nervous system. The anticonvulsant effects of benzodiazepines could be due in part or whole to their binding to voltage-dependent sodium channel receptors rather than to benzodiazepine receptors.