Amfecloral

Amfecloral
Clinical data
Trade namesAcutran
Other namesalpha-methyl-N-(2,2,2-trichloroethylidene)phenethylamine;
N-(2,2,2-trichloroethylidene)amphetamine
Drug class
ATC code
  • none
Legal status
Legal status
  • In general: unscheduled
Identifiers
  • 2,2,2-trichloro-N-(1-phenylpropan-2-yl)ethanimine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H12Cl3N
Molar mass264.57 g·mol−1
3D model (JSmol)
  • ClC(Cl)(Cl)/C=N/C(Cc1ccccc1)C
  • InChI=1S/C11H12Cl3N/c1-9(15-8-11(12,13)14)7-10-5-3-2-4-6-10/h2-6,8-9H,7H2,1H3/b15-8+ Y
  • Key:VBZDETYCYXPOAK-OVCLIPMQSA-N Y
 NY (what is this?)  (verify)

Amfecloral (INN) or amphecloral (USAN) is a combination drug containing a central nervous system (CNS) stimulant and anorectic drug, dextroamphetamine, as well as a CNS depressant and sedative-hypnotic, chloral hydrate.

Widely used for its anorectic properties, amfecloral was approved by the United States Food and Drug Administration as an anti-obesity drug and marketed and distributed under the brand name Acutran. Upon 1962 passage of the Kefauver-Harris Amendment, pressure grew to withdraw the product from the market, and in 1973, production ceased for Acutran and its generic formulation, concurrent with similar combination anorectics, Desbutal (methamphetamine-pentobarbital) and Obetrol (methamphetamine-dextroamphetamine).

Naming and Classification

The British Pharmacopoeia Commission approved the name amfecloral in 1970.[2] It is classified as a combination drug constituting active ingredients belong to the phenethylamine and ethanol chemical classes, similar to many combination drugs in widespread use at the time for various indications, including Desbutal, Dexamyl (also branded AmoDex), and Obetrol. Amfecloral belongs to the phenethylamine and substituted amphetamine chemical classes.

Synthesis and Pharmacology

The raw ingredients used in manufacturing it were dextroamphetamine and chloral hydrate.[3]

Upon ingestion and metabolization, amfecloral is metabolized as dextroamphetamine and chloral hydrate, as well as converting into levoamphetamine, the R enantiomer of amphetamine.[4] Amphetamine is a stimulant, whereas chloral hydrate is a sedative/hypnotic drug.[5]

The extent of metabolism and in-vivo contribution of a chloral hydrate metabolism to its purported "little to no stimulant activity" is unknown.

History

Combination Drugs in the Twentieth Century

Acutran was one of several brands, amfecloral one of several formulations distributed as anorectic combination drugs comprising a CNS stimulant and a CNS depressant–respectively known as "uppers" and "downers" in common parlance, conjoined in the form of one pill: others included Desbutal (methamphetamine-pentobarbital) and Obetrol (meth-dexamphetamine), both of which were discontinued concurrent to Acutran in 1973; Eskatrol (amphetamine and the neuroleptic compazine, discontinued 1981), in addition to Dexamyl (dextamphetamine-amylbarbitone).[1]

Efficacy and Tolerability

A review from 1970 specified that amfecloral was unique among amphetamine-like substances in that it displayed little to no stimulant activity, likely due to the powerful sedating effects of chloral hydrate, the same claims were not made of the other combination medications.[6]

The extent of metabolism and in-vivo contribution of a chloral hydrate metabolism to its purported "little to no stimulant activity" is unknown.

Discontinuation

Following increased scrutiny of combination medications comprising psychostimulant and sedative components with the 1962 passage of the Kefauver-Harris Amendment, then the Controlled Substances Act of 1970, Acutran was withdrawn from the U.S. pharmaceutical market and ceased production, alongside Desbutal (methamphetamine-pentobarbital) and Obetrol (methamphetamine-dextroamphetamine), all three of which were fully discontinued by the end of 1973.

See also

References

  1. ^ a b Ganellin CR, Triggle DJ (1996). Dictionary of pharmacological agents, Volumes 1-2. Chapman & Hall. p. 67. ISBN 9780412466304.
  2. ^ "Notes and News". The Lancet. 296 (7675): 730–732. October 1970. doi:10.1016/S0140-6736(70)92010-6.
  3. ^ McPherson EM (2007). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Burlington: Elsevier. p. 244. ISBN 9780815518563.
  4. ^ "NCATS Inxight Drugs — AMFECLORAL, (+)-". drugs.ncats.io. Retrieved 2024-07-16.
  5. ^ Pagel JF, Parnes BL (June 2001). "Medications for the Treatment of Sleep Disorders: An Overview". Primary Care Companion to the Journal of Clinical Psychiatry. 3 (3): 118–125. doi:10.4088/pcc.v03n0303. PMC 181172. PMID 15014609.
  6. ^ Van Rossum JM (1970). "Mode of action of psychomotor stimulant drugs". International Review of Neurobiology. 12: 307–83. doi:10.1016/s0074-7742(08)60065-3. ISBN 9780123668127. PMID 4918147.
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.