Abstract

Phenazepam is a type of benzodiazepine drug that causes central nervous system (CNS) depression and is commonly used to treat insomnia and anxiety. While it is currently a prescription medication in Russia and other Commonwealth of Independent States (CIS) countries, it has recently become available on the illicit drug market in the United Kingdom and United States. Phenazepam can be found in the form of powder, solution in dropper bottles, or tablets. It has also been observed in combination with synthetic cannabinoids in smokeable herbal products and on blotter papers. Phenazepam is considered a psychosedative.

Phenazepam, also known as bromdihydrochlorphenylbenzodiazepine, was developed in the Soviet Union in 1975 and is now produced in Russia and some CIS countries. This article provides a comprehensive overview of Phenazepam, including its general information, physico-chemical properties, recreational use pharmacology, effects and symptoms, hepatotoxicity, street names, prices, and approximate dosage, dangerous interactions, legal status, synthesis, conclusion, and bibliography.

First Time – Priceless Warning – A Phenazepam Trip Report

General Information About Phenazepam [1, 2]

Other synonyms and trading names of Phenazepam are: Fenazepam; Phenazapam; PHENZITAT;

IUPAC Name of : 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one

CAS numbers are 66173-95-3; 51753-57-2

Some different analogs of Phenazepam are: 4′-Chlorodiazepam; Bromazepam; 7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one; Clonazepam; Clorazepate; Clotiazepam; Nordazepam; Diazepam; Fludiazepam; Lorazepam; Nitrazepam etc.

Physico-Chemical Properties of Phenazepam [1, 2, 3]

• Molecular Formula C₁₅H₁₀BrClN₂O
• Molecular Weight 349.61
• Boiling point 493.0±45.0 °C at 760 mmHg https://safrole.com/knowledge-base/boiling-point-definition/
• Melting Point 220-222 °C https://safrole.com/knowledge-base/the-melting-point-definition/
• Color/Form: White Powder

Structural formula present on Figure 1.

Solution and powder possible of the Phenazepam can be seen in the pictures provided in Figure 2 and Figure 3.

General Information of Phenazepam in Recreational Use and Pharmacology [4]

Phenazepam is a potent agonist of the gamma-aminobutyric acid-A (GABAA) receptor, resulting in CNS depression. Anxiolytic effects have been observed in male rats at very low doses of phenazepam, as demonstrated in plus-maze and conflict tests. At conventional doses, phenazepam acts as a strong tranquilizer. In tests conducted on adult rats trained to discriminate pentobarbital versus saline, phenazepam fully substituted for pentobarbital. The selective benzodiazepine antagonist flumazenil fully antagonized the discriminative effects of phenazepam in antagonism tests. 3-Hydroxyphenazepam, a metabolite of phenazepam, is also a GABA receptor agonist, indicating a high overdose potential.

Overdose of phenazepam can lead to adverse effects, such as loss of coordination, retrograde amnesia, dizziness, drowsiness, respiratory depression, and coma. Death from phenazepam ingestion alone is rare, but can occur if phenazepam is ingested with another CNS depressant, such as opioids or alcohol, that has synergistic effects. There is limited information on the pharmacokinetics and metabolism of phenazepam in humans. After oral dosing with 3 mg or 5 mg, phenazepam has a peak plasma concentration between 200 and 400 µg l^-1 at approximately 4 hours, with a slow elimination half-life of about 60 hours, which may encourage users to re-dose prior to experiencing its effects.

Phenazepam is also abused recreationally for its euphoric effects, to enhance the effects of opioids, and to alleviate withdrawal symptoms. Additionally, it has been reported that phenazepam can be used to modulate the effects of cocaine and alcohol.

Effects and symptoms of Phenazepam Use [5]

In addition to the common side effects, there have also been reports of more severe adverse effects associated with phenazepam use. These include respiratory depression, seizures, and even death in cases of overdose or when combined with other CNS depressants. Due to the potential for abuse and the serious health risks associated with its use, phenazepam has been classified as a controlled substance in many countries, including the United States, Canada, and the United Kingdom.

In terms of detection in biological samples, phenazepam can be detected in urine and blood for up to several days after use, depending on the dose and frequency of use. It can also be detected in hair samples for up to several months after use. In cases of suspected phenazepam overdose or abuse, toxicology testing can provide important information for medical treatment and legal purposes.

Overall, phenazepam is a potent benzodiazepine with a high potential for abuse and serious health risks associated with its use. It is important for healthcare providers and the general public to be aware of these risks and to take appropriate measures to prevent its misuse and abuse.

Street Names, Prices and Approximate Dosage [4, 5, 6]

Phenazepam is a benzodiazepine known by various street names including Bonsai, Soviet Benzo, Fenaz, and Panda. In Russia and other CIS countries, phenazepam is a legitimate pharmaceutical drug; however, in the United States, it is used recreationally. The drug is reportedly used by various age groups, including youths, young adults, and older adults. The clinical dose of phenazepam depends on the condition being treated but does not usually exceed 5-10 mg per day. Illicitly, phenazepam is sold as a powder or tablets and has been found spiked in LSD mimic blotters in the USA and mixed with synthetic cannabinoids in New Zealand. Recreational doses are typically between 2-10 mg, but some users may take higher amounts. Phenazepam can be taken orally or snorted and provides a sedative effect that can relieve anxiety and promote relaxation. However, the drug can also cause dizziness, loss of coordination, and drowsiness. High doses can lead to forgetfulness, sleep, or even coma.

Dangerous interactions [7]

Phenazepam is a potent benzodiazepine with a high risk of overdose. Taking too much can lead to hospitalization or even death. It is important to be aware of the risks involved when taking phenazepam. Mixing it with other depressant drugs like heroin, other tranquilizers, or alcohol can increase the risk of an accidental overdose. It can take a few hours for the effects of phenazepam to be felt, so re-dosing before feeling the effects can be dangerous and increase the risk of overdose. Unfortunately, phenazepam is sometimes used to create fake Valium (diazepam), which can lead to people unknowingly taking a high dose of phenazepam and ending up in the hospital. Combining phenazepam with alcohol is particularly dangerous as it can lead to an accidental overdose and potentially death. Phenazepam and other benzodiazepines can cause serious addiction, both psychological and physical, leading to increased tolerance and the need for higher doses to achieve the same effect. If used for a prolonged period of time, withdrawal symptoms such as anxiety, insomnia, and tremors can occur, and they can persist for a long time, as with all minor tranquilizers.

Legal Status [2]

Benzodiazepines are commonly prescribed medications, but phenazepam currently has no approved medical use in the United States. Developed in the Soviet Union, phenazepam has been used since 1978 to treat neurological conditions such as epilepsy, anxiety, alcohol withdrawal syndrome, and sleep disorders. It is available in the form of 0.5 mg and 1.0 mg tablets, 0.1% and 0.3% injectable solutions, or transdermal patches in countries where it is marketed for clinical use. Despite its widespread use, phenazepam is not currently classified as a controlled substance under the Controlled Substances Act (CSA) in the United States, except in Louisiana where it is listed as Schedule I. It is also not approved by the FDA. In other countries, phenazepam is classified as a controlled substance, such as in Russia where it is listed as Schedule III of psychotropics, and in China where it became a controlled substance in October 2015. Finland classified phenazepam as a narcotic in July 2014, while Norway added it to the Regular Narcotic List in March 2010. As of March 22, 2021, Russia now requires phenazepam to be classified as a controlled substance. In Estonia, phenazepam is classified as a Schedule IV substance under the Narcotic Drugs and Psychotropic Substances Act.

Synthesis of 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one [8]

Like other benzodiazepines, phenazepam (7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one) is composed of a benzene ring fused to a seven-membered 1,4-diazepine ring. A 2-chlorophenyl ring is attached at the 5-position and a bromine is attached at the 7-position. First, 2-(o-chlorobenzoylamino)-5-bromo-2-chlorobenzophenone is prepared by acylation of p-bromoaniline with o-chlorobenzoic acid acyl chloride in the presence of a zinc chloride catalyst. This is hydrolysed with aqueous sulfuric acid to yield 2-amino-5-bromo-2′-chlorobenzophenone, which is then acylated with hydrochloride of aminoacetic acid acyl chloride in chloroform to form 2-(aminomethylkarbonylamino)-5-bromo-2-chlorobenzophenone hydrochloride, which is converted to a base with aqueous ammonia and then thermally cyclized to bromodihydrochlorophenylbenzodiazepine (phenazepam) (Figure 4). Hydrochloride of aminoacetic acid acyl chloride is prepared by chemical treating glycine with phosphorus pentachloride (PCl₅) in chloroform.

Conclusion

Phenazepam is a benzodiazepine that is increasingly being abused in Western Europe and the United States. In Russia and other CIS countries, phenazepam is a legitimate pharmaceutical drug. It is believed to be more potent than the commonly abused benzodiazepine diazepam, and its side effects are more severe and longer-lasting. When used recreationally, it can impair judgment, particularly while driving or operating machinery. It is anticipated that severe toxicity could result from the concurrent use of other central nervous system depressants, particularly opioids and alcohol. Standard laboratory techniques can be used to detect and quantify phenazepam in biological fluids. Recreational doses of phenazepam are typically reported to be between 2-10 mg, although sometimes higher. It is important to note that phenazepam is often used to produce counterfeit Valium (diazepam). It is critical not to combine phenazepam with alcohol or other depressant drugs, as this could result in an accidental overdose and potentially lead to death.

Bibliography

1. https://pubchem.ncbi.nlm.nih.gov/compound/40113#section=Computed-Properties
2. https://en.wikipedia.org/wiki/Phenazepam
3. https://www.chemspider.com/Chemical-Structure.36657.html
4. Drug Enforcement Administration. PHENAZEPAM. https://www.deadiversion.usdoj.gov/drug_chem_info/phenazepam.pdf
5. Peter D., Giorgia De Paoli etc. Phenazepam: The drug that came in from the cold. Journal of Forensic and Legal Medicine, 2012, 19, 122-125. doi:10.1016/j.jflm.2011.12.014 https://pubmed.ncbi.nlm.nih.gov/22390996/
6. Jon B. Stephenson, David E. Golz and Mary Jo Brasher Phenazepam and its Effects on Driving. Journal of Analytical Toxicology, 2012, Volume 37, Issue 1, Pages 25–29. https://doi.org/10.1093/jat/bks080 https://academic.oup.com/jat/article/37/1/25/746994?login=false
7. https://www.talktofrank.com/drug/phenazepam#the-risks
8. Synthetic pharmaceutical drugs (in Russian). Moscow: Medicine. 1983. pp. 215–216.