Editorial-Announcement

Editorial-Announcement

Published Date: 2021-09-16

Emanuel M. Kulich^*

Department of Mechatronics and Robotics, Sahlgrenska University Hospital, Gothenburg, Sweden

*Corresponding Author:: Emanuel M. Kulich
Department of Mechatronics and Robotics, Sahlgrenska University Hospital, Gothenburg, Sweden
Tel: 46725193481
E-mail: Emanuel@kulich.m

Received Date: March 15,2021; Accepted Date: September 06,2021; Published Date: September 16,2021

Citation: Emanuel M K(2021). Flualprazolm: A Critical Review Report. J Med Toxicol Clin Forensic Med Vol:7 No:5.

Visit for more related articles at Journal of Medical Toxicology and Clinical Forensic Medicine

Abstract

Journal of Medical Toxicology and Clinical Forensic Medicine is a Scholarly Open Access scientific journal which deals with both toxicology and Forensic medicine. Medical Toxicology is nothing but a medical subspecialty concentrating on the analysis, supervision and prevention of harming and additional adversative health issues due to medicines, workrelated and ecological contaminants, and organic causes. Clinical Forensic Medicine (CFM) is a health field which deals with the collaboration of clinical medicine and the law. Forensic analysis studies the arranged information with respect to events of occurred crime. Forensic analysis is used to determine and understand the outlines of the total activities. The data from claim organizations or from their original files is stated to as arranged data. Formless data in comparison is taken from statement and applications or from mobile expedients. This data has no all-embracing configuration and investigation there of means relating keywords or plotting message arrangements. Study of formless information is generally called to as Computer forensics. The analysis of huge sizes of information is usually implemented in a distinct record arrangement run by the investigation crew. Active organizations are generally not dimensioned to course broad separate analysis without disturbing the consistent customers. Forensic Analysis is systematically desirable to examine data duplicates on distinct systems and safeguard the analysis crews contrary to the allegation of changing unique data. Criminal investigation is an earliest science that might have origins as far-off as circa 1700 BCE in the literatures of the Code of Hammurabi. In the code it is recommended that equally the accuser and accused had the correct to present proof they collected. In the current era criminal research are most frequently done by government police forces. Private investigators are also usually employed to ample or assist in criminal investigations

Introduction

Substance Identification

• (UNII) FWF5L8D2BE

• CAS Number: 28910-91-0

• C17H12ClFN4

• None. Flualprazolam does not currently have an accepted medical use.

• 2’-Fluoro Alprazolam, ortho-Fluoro Alprazolam

• Flualprazolam, Flualp

• Flualprazolam is primarily a white or sometimes of-white powder.

Chemistry

Chemical Name

• 8-chloro-6-(2-fuorophenyl)-1-methyl-4Hbenzo[f] [1,2,4]triazolo[4,3-a] [1,4]diazepine.

• 28910-91-0

• 10359044

Chemical Structure

Flualprazolam is a substance of the benzodiazepine class. Benzodiazepines contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R1 and R4. The benzyl ring of fualprazolam is substituted at R8 with a chlorine group. Furthermore, the diazepine ring is bonded at R5 to a phenyl ring. The only, but key diference to alprazolam is a fuorine group located at R2'. Flualprazolam also contains a 1-methylated triazole ring fused to and incorporating R1 and R2 of its diazepine ring. Flualprazolam can also be described as the 2'- fuoro derivative of alprazolam, or the fuoro - instead of chloro - analogue of triazolam. When benzodiazepines contain a fused triazole ring like this, they are called triazolobenzodiazepines, distinguished by the sufx "-zolam".

• C17H12ClFN4

• 326.8 g/mol

Free base skeletal structure

Synthesis

There are many ways to synthesise Fluaprazolam. This has resulted in an abundance of laboratories manufacturing it for research purposes. It is therefore also widely accessible through online retailers. Syntheses of several triazolo-benzodiazepines were initially described in the patent application by J. Hester Jr. in 1976. More recently however, alternate methods for synthesizing alprazolam have been published which include the formation and preparation of fualprazolam as an intermediary in the process of synthesizing other benzodiazepines (Fustero et al., 2006). Fustero et al. (2006) describes three routes, indicating alternative methods to produce the triazolobenzodiazepines: alprazolam, triazolam, or midazolam. Fundamentally, alprazolam and triazolam are structurally similar to fualprazolam. The R1 is simply replaced with a fuorine atom.

Chemical Properties

• No data.

• Partially soluble (National Forensic Laboratory (NFL) Slovenia, 2018).

Ease of Convertibility into Controlled Substances

At the time of writing, there are currently no published data specifcally regarding the ease of convertibility of fualprazolam to other controlled substances. However, the process is described for the formation of fualprazolam (Fustero et al., 2006) as an intermediary in the process of synthesizing other similarly structured benzodiazepines such as alprazolam. As a result, fualprazolam might be converted into a controlled substance such as alprazolam. Alprazolam is Schedule IV substance as per the 1971 convention on Psychotropic Substances.

General Pharmacology

Routes of administration and dosage According to the published literature of Zawilska and Wojcieszak (2019) and that of Moosmann and Auwarter (2018), oral doses of 125 μg up to 2 mg are described. Moreover, an experience report from the online forum Reddit, described doses in the range of 250 μg up to 500 μg.

Pharmacokinetics

Flualprazolam is classifed as a benzodiazepine. More specifcally, a triazolo-benzodiazepine. Triazolobenzodiazepines difer structurally from benzodiazepines such as diazepam. This explains their distinct diferences in pharmacological activity, duration of onset and course of efect, which is described by Garzone and Kroboth (1989). Information on the specifc pharmacokinetics of fualprazolam are scarce. However, information on the structurally similar 1,4- triazolobenzodiazepines, alprazolam and triazolam is widely available. According to the published literature, both alprazolam and triazolam possess high afnities for the benzodiazepine receptor as Garzone and Kroboth (1989) state.

Peak concentrations of alprazolam and triazolam occur within an hour of ingestion, which suggests that they have a highly rapid absorption. The volume of distribution of alprazolam and triazolam is approximately the same: 1 L. Both of these triazolobenzodiazepines display high binding afnity to plasma proteins. Alprazolam has a plasma protein binding afnity of 70% and triazolam approximately 85%. Alprazolam’s mean elimination half-life (in healthy adults) ranges from 9.5 to 12 hours according to Garzone and Kroboth (1989). Liver disease can prolong the elimination of Alprazolam, but kidney disease does not seem to do the same.

Flualprazolam’s onset of action is reported to be 10 - 30 min, with a total duration 6 - 14h, according to Zawilska and Wojcieszak (2019). An individual experience report from the online forum Reddit, suggests the onset of action is approximately 30 - 40minutes. The 1,4-triazolo ring prevents oxidative metabolism of classical benzodiazepines. This results in the formation of active metabolites with a much longer elimination half-life.

Pharmacodynamics

Unfortunately, only very limited descriptions of the subjective efects of fualprazolam are available. Another online experience report from the online forum Reddit, described feeling efects such as: sedition and impairment. These efects are likely produced in a similar way to other benzodiazepines. They produce their efects via allosteric modulation of the GABA reception, potentiating the action of GABA. This leads to sedative efects and impairment.

In the patent application of J. Hester Jr. (1976), he only reports the acute and pre-clinical efects of alprazolam. Other preclinical studies indicate that fualprazolam demonstrated sedative efects in the following tests: Chimney Test done with intraperitoneal (IP) doses of 0.09 mg/kg Sedative dose in the Dish test of 0.15 ng/kg with IP administration, or 0.045 mg/kg when administered orally. Sedative/tranquilizing efects were reported on the Pedestal Test at IP doses of 0.20 mg/kg or oral doses of 0.9 mg/kg. Flualprazolam has shown indications in protection against nicotine induced convulsions, tonic extensor fts, and death at doses of 0.04mg/kg (oral). It had muscle relaxant or antispasmodic activity against the efects of strychnine administration at 1 mg/kg.

Toxicology

At the time of writing, no preclinical studies have been identifed that examine the acute toxicity or chronic health efects of fualprazolam or its metabolites either in animals or humans.

The United Nations Ofce on Drugs and Crime’s (UNODC) early warning advisory on “new psychoactive substances” included 42 reports that involved fualprazolam. These reports predominantly represented people aged 15-24 years old (26 of 42 cases), and predominantly male (37 of 42 cases). Forty of the 42 cases were reported in the USA with two cases from Finland. In fve cases the samples were documented to have been collected post mortem and 21 were noted to be ante-mortem samples. The remaining cases had no additional information on context.” (World Health Organization, Expert Committee on Drug Dependence, 2019).

Adverse Reactions In Humans

There are only a limited number of reports that document adverse reactions with fualprazolam. This is likely to be due to the lack of availability of registered therapeutic products. As such, there is currently no published literature covering the potential adverse reactions. However, it is likely so that the adverse reactions of fualprazolam would closely resemble those of alprazolam, due to its similar potency, onset of action and half-life. Given its structural similarity, fualprazolam is thought to have similar sedative efects.

Dependence Potential

• No animal studies could be identified.

• No human studies could be identifed that specifcally study the dependence potential of fualprazolam in humans.

Abuse Potential

• No animal studies could be identified

• No human studies could be identifed that describe abuse liability.

Non-Medical Use, Abuse And Dependence

A report from the online forum Reddit, describes nonmedical use of fualprazolam (with pellets purchased online). It is reported to produce similar efects to clonazepam and alprazolam. This report is consistent with preclinical studies described in the patent application by J Hester Jr. (1976) demonstrating sedative/tranquilizer and muscle relaxant efects.

Industrial Use

No known industrial use. However, large-scale syntheses and production of Flualprazolam for sale through online research chemical retailers has recently grown in popularity.

Licit Production, Consumption And International Trade

Large quantities of fualprazolam are produced by numerous laboratories for research use. Flualprazolam is thus readily available through online research chemical retailers. Information on the synthesis and preparation of fualprazolam is contained in the patent application (Hester, 1976), and is also published by Fustero et al. (2006).

Current International Controls And Their Impact

Flualprazolam is not controlled under the 1961, 1971 or 1988 United Nations Conventions.