Diazepam

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Diazepam
Clinical data
Pronunciation/dˈæzɪpæm/ dy-AZ-ip-am
Trade namesValium, Vazepam, Valtoco, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa682047
License data
Pregnancy
category
Dependence
liability
High[3]
Addiction
liability
Moderate[4][5]
Routes of
administration
oral, intramuscular, intravenous, rectal, nasal[6]
Drug classBenzodiazepine
ATC code
Legal status
Legal status
desmethyldiazepam, CYP2C19 (major route) to inactive metabolites, CYP3A4 (major route) to desmethyldiazepam
Elimination half-life(50 h); 20–100 h (32–200 h for main active metabolite desmethyldiazepam)[10][8][9]
ExcretionKidney
Identifiers
  • 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one[1]
JSmol)
  • c1ccccc1C2=NCC(=O)N(C)c3ccc(Cl)cc23
  • InChI=1S/C16H13ClN2O/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3 checkY
  • Key:AAOVKJBEBIDNHE-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Diazepam, first marketed as Valium, is a medicine of the

muscle spasms, insomnia, and restless legs syndrome.[12] It may also be used to cause memory loss during certain medical procedures.[13][14] It can be taken orally (by mouth), as a suppository inserted into the rectum, intramuscularly (injected into muscle), intravenously (injection into a vein) or used as a nasal spray.[6][14] When injected intravenously, effects begin in one to five minutes and last up to an hour.[14] Orally, effects begin after 15 to 60 minutes.[15]

Common side effects include sleepiness and trouble with coordination.

Diazepam was patented in 1959 by

Hoffmann-La Roche.[12][19][20] It has been one of the most frequently prescribed medications in the world since its launch in 1963.[12] In the United States it was the best-selling medication between 1968 and 1982, selling more than 2 billion tablets in 1978 alone.[12] In 2021, it was the 149th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[21][22] In 1985, the patent ended, and there are more than 500 brands available on the market.[12] It is on the World Health Organization's List of Essential Medicines.[23]

Structure, physical and chemical properties

Diazepam does not possess any chiral centers in its structure, but it does have two conformers. The two conformers mentioned were the 'P'-conformer and 'M'-conformer. Diazepam is an equimolar mixture and it was shown through CD spectra in serum protein solutions, that the 'P'-conformer is preferred by α1-acid glycoprotein binding.

The drug diazepam occurs as a pale yellow-white crystalline powder without distinctive smell and has a low molecular weight (MW = 284,74 g/mol[13]). This classic aryl 1,4-benzodiazepine possesses three acceptors and no hydrogen bond donors. Diazepam is moderately lipophilic with LogP (Octanol-Water Partition Coefficient) value of 2,82 and hydrophilic with a TPSA (Topological Polar Surface Area) value of 32.7 Ų.[13] The LogP value indicates that diazepam has a tendency to dissolve more readily in lipid-based environments, such as chloroform, acetone, ethanol and ether, compared to water. While the TPSA value implies that a segment of the molecule exhibits a degree of polarity or hydrophilicity and represents the collective surface area of polar atoms, like oxygen or nitrogen, along with their connected hydrogen atoms. A TPSA value of 32,7 Ų signifies a moderate level of polarity within the compound. TPSA is especially useful in medical chemistry as it shows the ability of a molecule to permeate cells. Molecules with PSA value smaller than 60-70 Ų has a better ability to permeate cells.[24] The balance between its lipophilic and hydrophilic characteristics can impact various aspects of the molecule’s behavior, including its solubility, absorption, distribution, metabolism, and potential interactions within the biological system.

Diazepam is overall a stable molecule. The

United States Pharmacopoeia lists diazepam as soluble 1 in 16 ethyl alcohol, 1 in 2 of chloroform, 1 in 39 ether, and practically insoluble in water. The pH of diazepam is neutral (i.e., pH = 7). Due to additives such as benzoic acid/benzoate in the injectable form.[clarification needed][25] Diazepam has a shelf life of five years for oral tablets and three years for IV/IM solutions.[26]
Diazepam should be stored at room temperature (15–30 °C). The solution for parenteral injection should be protected from light and kept from freezing. The oral forms should be stored in air-tight containers and protected from light.[27]

Diazepam can absorb into plastics, so liquid preparations should not be kept in plastic bottles or syringes, etc. As such, it can leach into the plastic bags and tubing used for intravenous infusions. Absorption appears to depend on several factors, such as temperature, concentration, flow rates, and tube length. Diazepam should not be administered if a precipitate has formed and does not dissolve.[27]

Medical uses

Diazepam tablets (10, 5, and 2 mg)

Diazepam is mainly used to treat anxiety, insomnia, panic attacks and symptoms of acute alcohol withdrawal. It is also used as a premedication for inducing sedation, anxiolysis, or amnesia before certain medical procedures (e.g., endoscopy).[28][29] In 2020, it was approved for use in the United States as a nasal spray to interrupt seizure activity in people with epilepsy.[6][30] Diazepam is the most commonly used benzodiazepine for "tapering" benzodiazepine dependence due to the drug's comparatively long half-life, allowing for more efficient dose reduction. Benzodiazepines have a relatively low toxicity in overdose.[17]

Diazepam has a number of uses, including:

Used in treatment of organophosphate poisoning and reduces the risk of seizure induced brain and cardiac damage.

  • Preventive treatment of
    hyperbaric oxygen therapy[37]

Dosages should be determined on an individual basis, depending on the condition being treated, severity of symptoms, patient body weight, and any other conditions the person may have.[26]

Seizures

Intravenous diazepam or lorazepam are first-line treatments for status epilepticus.[17][38] However, intravenous lorazepam has advantages over intravenous diazepam, including a higher rate of terminating seizures and a more prolonged anticonvulsant effect. Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures.[39] Diazepam is rarely used for the long-term treatment of epilepsy because tolerance to its anticonvulsant effects usually develops within six to twelve months of treatment, effectively rendering it useless for that purpose.[26][40]

The anticonvulsant effects of diazepam can help in the treatment of seizures due to a drug overdose or chemical toxicity as a result of exposure to sarin, VX, or soman (or other organophosphate poisons), lindane, chloroquine, physostigmine, or pyrethroids.[26][41]

Diazepam is sometimes used intermittently for the prevention of

febrile seizures that may occur in children under five years of age.[17] Recurrence rates are reduced, but side effects are common so the decision to treat febrile seizures (which are benign in nature) with medication should use this as part of the evaluation.[42] Long-term use of diazepam for the management of epilepsy is not recommended; however, a subgroup of individuals with treatment-resistant epilepsy benefit from long-term benzodiazepines, and for such individuals, clorazepate has been recommended due to its slower onset of tolerance to the anticonvulsant effects.[17]

Alcohol withdrawal

Because of its relatively long duration of action, and evidence of safety and efficacy, diazepam is preferred over other benzodiazepines for treatment of persons experiencing moderate to severe alcohol withdrawal.

intramuscular in which case either lorazepam or midazolam is recommended.[43]

Other

Diazepam is used for the emergency treatment of eclampsia, when IV magnesium sulfate and blood-pressure control measures have failed.[44][45] Benzodiazepines do not have any pain-relieving properties themselves, and are generally recommended to avoid in individuals with pain.[46] However, benzodiazepines such as diazepam can be used for their muscle-relaxant properties to alleviate pain caused by muscle spasms and various dystonias, including blepharospasm.[47][48] Tolerance often develops to the muscle relaxant effects of benzodiazepines such as diazepam.[49] Baclofen is sometimes used as an alternative to diazepam.[50]

Availability

Diazepam is marketed in over 500 brands throughout the world.[51] It is supplied in oral, injectable, inhalation, and rectal forms.[26][27][52]

The

nerve agents are considered a potential hazard. Both of these kits deliver drugs using autoinjectors. They are intended for use in "buddy aid" or "self aid" administration of the drugs in the field prior to decontamination and delivery of the patient to definitive medical care.[53]

Contraindications

Use of diazepam should be avoided, when possible, in individuals with:[54]

Caution

  • Benzodiazepine abuse and misuse should be guarded against when prescribed to those with alcohol or drug dependencies or who have
    psychiatric disorders.[56]
  • Pediatric patients
  • Elderly and very ill patients can possibly experience apnea or cardiac arrest. Concomitant use of other central nervous system depressants increases this risk. The smallest possible effective dose should be used for this group of people.[57][58] The elderly metabolise benzodiazepines much more slowly than younger adults, and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. Doses of diazepam are recommended to be about half of those given to younger people, and treatment limited to a maximum of two weeks. Long-acting benzodiazepines such as diazepam are not recommended for the elderly.[17] Diazepam can also be dangerous in geriatric patients owing to a significant increased risk of falls.[59]
  • Intravenous or intramuscular injections in hypotensive people or those in shock should be administered carefully and vital signs should be monitored.[58]
  • Benzodiazepines such as diazepam are
    metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.[61]

Adverse effects

Benzodiazepines such as diazepam can cause anterograde amnesia, confusion, and sedation. The elderly are more prone to diazepam's confusion, amnesia, ataxia, hangover symptoms, and falls. Long-term use of benzodiazepines such as diazepam induces tolerance, dependency, and withdrawal syndrome.[17] Like other benzodiazepines, diazepam impairs short-term memory and learning new information. Diazepam and other benzodiazepines can produce anterograde amnesia, but not retrograde amnesia. It means information learned before using benzodiazepines is not impaired. Short-term benzodiazepine use does not lead to tolerance, and the elderly are more sensitive to them.[62] Additionally, after stopping benzodiazepines, cognitive problems may last at least six months; it is unclear if these problems last for longer than six months or are permanent. Benzodiazepines may also cause or worsen depression.[17] Infusions or repeated intravenous injections of diazepam when managing seizures, for example, may lead to drug toxicity, including respiratory depression, sedation and hypotension. Drug tolerance may also develop to infusions of diazepam if it is given for longer than 24 hours.[17] Sedatives and sleeping pills, including diazepam, have been associated with an increased risk of death.[63]

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[64]

Diazepam has a range of side effects common to most benzodiazepines, including:

Less commonly,

alcohol use disorder, or a history of aggressive behavior.[17][66][67][68] In some people, diazepam may increase the propensity toward self-harming behavior and, in extreme cases, may provoke suicidal tendencies or acts.[69] Very rarely dystonia can occur.[70]

Diazepam may impair the ability to drive vehicles or operate machinery. The impairment is worsened by consumption of alcohol, because both act as

During the course of therapy, tolerance to the sedative effects usually develops, but not to the anxiolytic and myorelaxant effects.[71]

Patients with severe attacks of

respiratory depression (hypoventilation), leading to respiratory arrest and death.[72]

Diazepam in doses of 5 mg or more causes significant deterioration in alertness performance combined with increased feelings of sleepiness.[73]

Tolerance and withdrawal

Diazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence, substance use disorder, and benzodiazepine withdrawal syndrome. Withdrawal from diazepam or other benzodiazepines often leads to withdrawal symptoms similar to those seen during barbiturate or alcohol withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms.[74]

Withdrawal symptoms can occur from standard dosages and also after short-term use, and can range from insomnia and anxiety to more serious symptoms, including seizures and psychosis. Withdrawal symptoms can sometimes resemble pre-existing conditions and be misdiagnosed. Diazepam may produce less intense withdrawal symptoms due to its long

elimination half-life.[43]

Benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen.

down-regulation of receptor sites, and desensitisation of receptor sites to the effect of GABA. About one-third of individuals who take benzodiazepines for longer than four weeks become dependent and experience withdrawal syndrome on cessation.[17]

Differences in rates of withdrawal (50–100%) vary depending on the patient sample. For example, a random sample of long-term benzodiazepine users typically finds around 50% experience few or no withdrawal symptoms, with the other 50% experiencing notable withdrawal symptoms. Certain select patient groups show a higher rate of notable withdrawal symptoms, up to 100%.[76]

Rebound anxiety, more severe than baseline anxiety, is also a common withdrawal symptom when discontinuing diazepam or other benzodiazepines.[77] Diazepam is therefore only recommended for short-term therapy at the lowest possible dose owing to risks of severe withdrawal problems from low doses even after gradual reduction.[78] The risk of pharmacological dependence on diazepam is significant, and patients experience symptoms of benzodiazepine withdrawal syndrome if it is taken for six weeks or longer.[79] In humans, tolerance to the anticonvulsant effects of diazepam occurs frequently.[80]

Dependence

Improper or excessive use of diazepam can lead to dependence. At a particularly high risk for diazepam misuse, substance use disorder or dependence are:

  • People with a history of a substance use disorder or substance dependence.[36][81] Diazepam increases craving for alcohol in problem alcohol consumers. Diazepam also increases the volume of alcohol consumed by problem drinkers.[82]
  • People with severe personality disorders, such as borderline personality disorder[83]

Patients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Therapy should be discontinued if any of these signs are noted, although if dependence has developed, therapy must still be discontinued gradually to avoid severe withdrawal symptoms. Long-term therapy in such instances is not recommended.[36][81]

People suspected of being dependent on benzodiazepine drugs should be very gradually tapered off the drug. Withdrawals can be life-threatening, particularly when excessive doses have been taken for extended periods of time. Equal prudence should be used whether dependence has occurred in therapeutic or recreational contexts.[84]

Diazepam is a good choice for tapering for those using high doses of other benzodiazepines since it has a long half-life thus withdrawal symptoms are tolerable.[85] The process is very slow (usually from 14 to 28 weeks) but is considered safe when done appropriately.[86]

Overdose

An individual who has consumed too much diazepam typically displays one or more of these symptoms in a period of approximately four hours immediately following a suspected overdose:[36][87]

  • Drowsiness
  • Mental confusion
  • Hypotension
  • Impaired motor function
    • Impaired reflexes
    • Impaired coordination
    • Impaired balance
    • Dizziness
  • Coma

Although not usually fatal when taken alone, a diazepam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The

The oral

desmethyldiazepam, oxazepam, and temazepam, according to samples taken in the hospital and as follow-up.[89]

Overdoses of diazepam with alcohol, opiates, or other depressants may be fatal.[88][90]

Interactions

If diazepam is administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that potentiate the effects of diazepam, such as barbiturates,

antidepressants.[36]

Diazepam does not increase or decrease hepatic enzyme activity, and does not alter the metabolism of other compounds. No evidence would suggest diazepam alters its own metabolism with chronic administration.[26]

Agents with an effect on hepatic

conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable.[26]

Pharmacology

5 mg Valium Roche packaging Australia

Diazepam is a long-acting "classical" benzodiazepine. Other classical benzodiazepines include

micromolar benzodiazepine binding sites as calcium channel blockers and significantly inhibit depolarization-sensitive calcium uptake in rat nerve cell preparations.[100]

Diazepam 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 diazepam in vivo. This may play a role in explaining diazepam's anticonvulsant properties.[101]

Diazepam binds with high affinity to

glial cells in animal cell cultures.[102] Diazepam at high doses has been found to decrease histamine turnover in mouse brain via diazepam's action at the benzodiazepine-GABA receptor complex.[103] Diazepam also decreases prolactin release in rats.[104]

Mechanism of action

Benzodiazepines are

limbic systems in the central nervous system is reduced.[1]

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 diazepam. 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.[105] Diazepam is not the only drug to target these GABAA receptors. Drugs such as flumazenil also bind to GABAA to induce their effects.[106]

Diazepam appears to act on areas of the limbic system, thalamus, and hypothalamus, inducing anxiolytic effects. Benzodiazepine drugs including diazepam increase the inhibitory processes in the cerebral cortex.[107]

The anticonvulsant properties of diazepam and other benzodiazepines may be in part or entirely due to binding to

voltage-dependent sodium channels rather than GABAA receptors. Sustained repetitive firing seems limited by benzodiazepines' effect of slowing recovery of sodium channels from inactivation.[108]

The muscle relaxant properties of diazepam are produced via inhibition of

polysynaptic pathways in the spinal cord.[109]

Pharmacokinetics

Diazepam can be administered orally, intravenously (must be diluted, as it is painful and damaging to veins), intramuscularly (IM), or as a suppository.[26]

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.

plasma protein-bound, with 96–99% of the absorbed drug being protein-bound. The distribution half-life of diazepam is two to 13 minutes.[17]

Diazepam is highly lipid-soluble, and is widely distributed throughout the body after administration. It easily crosses both the

adipose tissue. Continual daily doses of diazepam quickly build to a high concentration in the body (mainly in adipose tissue), far in excess of the actual dose for any given day.[17][26]

Diazepam 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 diazepam during pregnancy and breast feeding is clinically justified.[110]

Diazepam undergoes

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.[17] Most of the drug is metabolized; very little diazepam is excreted unchanged.[26] The elimination half-life of diazepam 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.[111]

Synthesis

The synthesis of Diazepam was first achieved through a reaction pathway developed by Leo Sternbach and his team at Hoffmann-La Roche in the late 1950s.

Sternbach's method commenced with 2-amino-5-chlorobenzophenone, which undergoes cyclocondensation with glycine ethyl ester hydrochloride to construct the benzodiazepine core. This core is subsequently alkylated at the nitrogen in the 1-position using dimethyl sulfate in the presence of sodium methoxide and methanol under reflux conditions. Although the direct transformation from 2-amino-5-chlorobenzophenone to Nordazepam is conceptually straightforward, an alternative approach involving the treatment of 2-amino-5-chlorobenzophenon with chloroacetyl chloride, succeeded by ammoniation and heating, culminates in Nordazepam with enhanced yield and facilitates easier purification processes. [112]

Detection in body fluids

Diazepam may be quantified in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest, or to assist in a medicolegal death investigation. Blood or plasma diazepam concentrations are usually in a range of 0.1–1.0 mg/L in persons receiving the drug therapeutically. Most commercial immunoassays for the benzodiazepine class of drugs cross-react with diazepam, but confirmation and quantitation are usually performed using chromatographic techniques.[113][114][115]

Environmental

Diazepam is a common

environmental contamination finding near human settlement.[116]

History

Diazepam was the second benzodiazepine invented by

Hoffmann-La Roche at the company's Nutley, New Jersey, facility[117] following chlordiazepoxide (Librium), which was approved for use in 1960. Released in 1963 as an improved version of Librium, diazepam became incredibly popular, helping Roche to become a pharmaceutical industry giant. It is 2.5 times more potent than its predecessor, which it quickly surpassed in terms of sales. After this initial success, other pharmaceutical companies began to introduce other benzodiazepine derivatives.[118]

The benzodiazepines gained popularity among medical professionals as an improvement over

depressants (such as alcohol or opioids).[88] Benzodiazepine drugs such as diazepam initially had widespread public support, but with time the view changed to one of growing criticism and calls for restrictions on their prescription.[119]

Marketed by Roche using an advertising campaign conceived by the William Douglas McAdams Agency under the leadership of

palliative treatment of certain types of epilepsy and spastic activity, for example, forms of paresis.[citation needed] It is also the first line of defense for a rare disorder called stiff-person syndrome.[35]

Society and culture

Recreational use

Diazepam is a medication with a high risk of misuse and can cause

drug dependence. Urgent action by national governments has been recommended to improve prescribing patterns of benzodiazepines such as diazepam.[122][123] A single dose of diazepam modulates the dopamine system in similar ways to how morphine and alcohol modulate the dopaminergic pathways.[124]
Between 50 and 64% of rats will self-administer diazepam.[125] Diazepam has been shown to be able to substitute for the behavioral effects of
barbiturates in a primate study.[126]
Diazepam has been found as an adulterant in heroin.[127]

Diazepam drug misuse can occur either through recreational misuse where the drug is taken to achieve a high or when the drug is continued long term against medical advice.[128]

Sometimes, it is used by stimulant users to "come down" and sleep and to help control the urge to binge. These users often escalate dosage from 2 to 25 times the therapeutic dose of 5 mg to 10 mg.[129]

A large-scale study in the US, conducted by

SAMHSA, using data from 2011, determined benzodiazepines were present in 28.7% of emergency department visits involving nonmedical use of pharmaceuticals. In this regard, benzodiazepines are second only to opiates, the study found in 39.2% of visits. About 29.3% of drug-related suicide attempts involve benzodiazepines, making them the most frequently represented class in drug-related suicide attempts. Males misuse benzodiazepines as commonly as females.[130]

Diazepam was detected in 26% of cases of people suspected of driving under the influence of drugs in Sweden, and its active metabolite nordazepam was detected in 28% of cases. Other benzodiazepines and zolpidem and zopiclone also were found in high numbers. Many drivers had blood levels far exceeding the therapeutic dose range, suggesting a high degree of potential for misuse for benzodiazepines, zolpidem, and zopiclone.[113] In Northern Ireland, in cases where drugs were detected in samples from impaired drivers who were not impaired by alcohol, benzodiazepines were found in 87% of cases. Diazepam was the most commonly detected benzodiazepine.[131]

Legal status

Diazepam is regulated as a

prescription medication
:

International

Diazepam is a Schedule IV controlled drug under the Convention on Psychotropic Substances.[132]

UK

Classified as a controlled drug, listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription, and for such purposes it is classified as a Class C drug.[133]

Germany

Classified as a prescription drug, or in high dosage as a restricted drug (Betäubungsmittelgesetz, Anlage III).[134]

Australia

Diazepam is a Schedule 4 substance under the Poisons Standard (June 2018).[135] A Schedule 4 drug is outlined in the Poisons Act 1964 as, "Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription".[135]

United States

Diazepam is controlled as a Schedule IV substance.[10]

Judicial executions

The states of California and Florida offer diazepam to condemned inmates as a pre-execution sedative as part of their lethal injection program, although the state of California has not executed a prisoner since 2006.[136][137] In August 2018, Nebraska used diazepam as part of the drug combination used to execute Carey Dean Moore, the first death row inmate executed in Nebraska in over 21 years.[138]

Veterinary uses

Diazepam is used as a short-term sedative and anxiolytic for cats and dogs,[139] sometimes used as an appetite stimulant.[139][140] It can also be used to stop seizures in dogs and cats.[141]

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Further reading

External links