Phenazepam

Summary

Phenazepam, also recognized as bromdihydrochlorphenylbenzodiazepine in Russia, belongs to the benzodiazepine class of drugs. Initially developed in the Soviet Union in 1975, it is currently manufactured in Russia and several associated countries.
Phenazepam serves various clinical purposes, notably in the treatment of mental disorders, including psychiatric schizophrenia and anxiety. Additionally, it finds application as a premedication before surgical procedures, enhancing the effects of anaesthetics. Notably, in recent times, phenazepam has gained popularity as a recreational substance. Reports of misuse have surfaced in different countries, including the United Kingdom, Finland, Sweden, and the United States.

Identifiers

IUPAC name
CAS Number	51753-57-2
PubChem CID	40113
ChemSpider	36657
UNII	3DSB43090Z
ChEMBL	ChEMBLCHEMBL1709464
CompTox Dashboard (EPA)	DTXSID00199685
ECHA InfoCard	100.207.405
Chemical and physical data
Formula	C15H10BrClN2O
Molar mass	349.61 g·mol−1

Indications

1. Various Conditions: Neurosis, neurosis-like conditions, psychopathic (personality disorder), psychopathic-like conditions, and other disorders characterized by fear, anxiety, heightened irritability, and emotional lability.
2. Specific Disorders: This includes brief reactive psychosis and hypochondriasis-senestopathic syndrome, along with vegetative dysfunction and vegetative lability.
3. Sleep Disturbances: It also encompasses the treatment of insomnia.
4. Alcohol Withdrawal: Phenazepam is utilized in managing alcohol withdrawal syndrome.
5. Seizure-Related Conditions: In some cases, phenazepam is employed in treating temporal lobe epilepsy and myoclonic epilepsy, although alternative options are preferred.
6. Motor Disorders: This includes conditions like hyperkinesia and tics, as well as muscle spasticity.
7. Treatment Duration: Typically, phenazepam therapy should not exceed two weeks. In exceptional cases, treatment may be extended up to two months to mitigate the risk of drug abuse and dependence. Gradual dose reduction is crucial to prevent withdrawal syndrome.

Chemistry

1. Chemical Structure: Phenazepam is classified as a benzodiazepine drug, characterized by a benzene ring fused to a diazepine ring. A bromine group is attached at the R7 position, and a chlorine substituent is present in the R2 group. A ketone is formed by a double bond to R2 of the diazepine ring, shared with other benzodiazepine drugs with the suffix -diazepam.
2. Molecular Composition: Phenazepam has a molecular formula of C15H10BrClN2O and a molecular weight of 349.6 g/mol.

Side Effects

1. Potential Side Effects: Common side effects may include hiccups, dizziness, loss of coordination, drowsiness, and noticeable anterograde amnesia, particularly at higher doses.
2. Withdrawal Symptoms: Abrupt discontinuation following prolonged use can lead to severe withdrawal symptoms, including restlessness, anxiety, insomnia, seizures, convulsions, and, in extreme cases, fatal outcomes. Due to its intermediate half-life, withdrawal symptoms may take several days to manifest.

Contraindications and Special Precautions

1. Special Precautions: When considering the use of benzodiazepines like phenazepam, it’s crucial to exercise caution in elderly individuals, during pregnancy, among children, in those with alcohol or substance dependence, and individuals with concurrent psychiatric disorders.
2. Interaction Risks: Phenazepam should not be taken with alcohol or other central nervous system depressants. It is generally not recommended for therapeutic use exceeding one month, in line with guidance for benzodiazepines in the British National Formulary. Some patients may require longer-term treatment.

Synthesis

1. Synthesis Process: The synthesis of phenazepam involves several steps, including the preparation of 2-(o-chlorobenzoylamino)-5-bromo-2-chlorobenzophenone, which is then hydrolyzed, acylated, and thermally cyclized to form bromodihydrochlorophenylbenzodiazepine, known as phenazepam.

Detection in Biological Fluids

1. Measuring Phenazepam: Phenazepam can be quantified in blood or plasma using chromatographic techniques. In therapeutic use, blood concentrations are typically below 30 μg/L, while impaired drivers arrested for this substance have been found with concentrations ranging from 100 to 600 μg/L.

Legal Status

1. China: As of October 2015, phenazepam is considered a controlled substance in China.
2. United States: Phenazepam is not classified as a controlled substance at the federal level. However, its sale for human use remains illegal in the United States. Some states have individually banned it.
3. United Kingdom: Phenazepam is classified as a Class C drug in the UK.
4. Global Regulation: Phenazepam’s legal status varies internationally. In Finland and Norway, it is considered a narcotic, while in Russia, it is available by prescription. As of March 2021, it is set to be controlled in Russia.
5. UN Single Convention on Narcotic Drugs: On 8 March 2016, Phenazepam was included in the schedules of the Convention on Psychotropic Substances of 1971 during the 59th Session of the Commission on Narcotic Drugs.

FAQ

1. What is Phenazepam?

Phenazepam is a benzodiazepine drug used for treating various mental health conditions, including anxiety and psychotic disorders. It is also known for its soothing effects.

2. What are the Common Uses of Phenazepam?

Phenazepam is employed to manage a range of conditions, including anxiety, sleep disturbances, and even alcohol withdrawal. It can also be used for specific seizure-related conditions and motor disorders.

3. What is the Recommended Treatment Duration for Phenazepam?

A course of treatment with Phenazepam typically should not exceed two weeks. In exceptional cases, therapy may be extended for up to two months. Prolonged use increases the risk of drug abuse and dependence.

4. What are the Chemical Characteristics of Phenazepam?

Phenazepam is a benzodiazepine with a complex chemical structure. It features a benzene ring fused to a diazepine ring and is distinguished by the presence of a bromine group at the R7 position.

5. What are the Side Effects of Phenazepam?

Common side effects include hiccups, dizziness, coordination issues, and drowsiness. At higher doses, noticeable anterograde amnesia may occur. Sudden discontinuation of Phenazepam can lead to severe withdrawal symptoms.

6. Is Phenazepam Safe for Everyone?

Like other benzodiazepines, Phenazepam requires special precautions. It should be used cautiously in the elderly, during pregnancy, and in individuals with comorbid psychiatric disorders or a history of substance dependence.

7. What is the Legal Status of Phenazepam in Various Countries?

The legal status of Phenazepam varies worldwide. It is considered a controlled substance in some countries like China and the UK, while in the United States, it is not a controlled substance at the federal level but is illegal for human use.

8. Is Phenazepam Available by Prescription?

In some countries, including Russia, Phenazepam is considered a prescription medication and can be obtained through medical channels. However, recent regulatory changes in Russia are affecting its availability.

9. How is Phenazepam Synthesized?

The synthesis of Phenazepam involves a multi-step chemical process, starting with the acylation of p-bromoaniline and culminating in the formation of bromodihydrochlorophenylbenzodiazepine.

10. Why was Phenazepam Banned in Some Products?

Phenazepam was found as an ingredient in certain products, such as “herbal incense”, in Australia and New Zealand. Due to its psychoactive properties and potential for misuse, these products were withdrawn from the market.

11. Is Phenazepam Covered by International Drug Control Agreements?

Yes, Phenazepam was added to the schedules of the Convention on Psychotropic Substances of 1971 during a session of the Commission on Narcotic Drugs. This underscores its regulation on the international level.

References

1. Louisiana Laws: Phenazepam is classified as a controlled dangerous substance in Louisiana. This designation was made to regulate the substance due to its potential for abuse and misuse.
2. Anvisa Regulations: The Brazilian National Health Surveillance Agency (Anvisa) issued Resolution No. 784, which lists Phenazepam as a substance under special control. This regulation outlines restrictions and controls on the sale and use of Phenazepam in Brazil.
3. Russian Restrictions: In Russia, Phenazepam is considered a prescription medication, but some pharmacies may sell it without requiring a prescription. However, starting from March 22, 2021, Phenazepam has been subjected to stricter control measures in Russia.
4. Pharmacokinetics: Studies have investigated the pharmacokinetics of Phenazepam when administered through transdermal therapeutic systems. These studies offer insights into how the drug is absorbed and distributed in the body.
5. In Vitro Metabolism: In vitro studies have explored the metabolism of Phenazepam. These experiments provide valuable information about how the drug is broken down and processed in the body.
6. World Health Organization: The World Health Organization (WHO) has likely addressed Phenazepam and its classification, although specific details about its recommendations are not mentioned in the source.
7. Misuse and Monitoring: Phenazepam has been reported as a substance of misuse in various countries, including Finland, Sweden, and the United States. Law enforcement and health agencies have monitored its usage.
8. Designer Benzodiazepines: Some studies have investigated the affinity of Phenazepam and other designer benzodiazepines for GABAA receptors, which are involved in their central nervous system-mediated effects.
9. Synthesis: The synthesis of Phenazepam is a multi-step process that was developed in the 1970s at the Physico-Chemical Institute of the Academy of Sciences of the Ukrainian SSR.
10. Detection in Biological Fluids: Phenazepam can be detected in blood or plasma using chromatographic methods. Blood concentrations can vary, depending on therapeutic use or other factors.
11. Legal Status in Various Countries: The legal status of Phenazepam varies globally. It is regulated differently in countries like China, the United States, the United Kingdom, Finland, Norway, and Estonia.
12. UN Single Convention: The United Nations Commission on Narcotic Drugs added Phenazepam to the schedules of the Convention on Psychotropic Substances of 1971, emphasizing international control measures.