The metabolic fate of 3H-fenetylline in man

Ellison, Theodore; Levy, Louis; Bolger, James W.; Okun, Ronald

doi:10.1016/0014-2999(70)90192-5

Cited by 39 publications

(15 citation statements)

References 2 publications

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“…It is possible that a strain difference in metabolism is responsible for the discrepancy or conceivably, urinary pH may have influenced excre tion of metabolites since it is known to affect excretion of unchanged am phetamine (119,120). Dring et al (118) and Ellison et al (121) also found that man metabolized the drug principally by deamination, like the rabbit and dog.…”

Section: Iuu Nesmentioning

confidence: 94%

Species Differences in Drug Metabolism

Hücker¹

1970

Annu. Rev. Pharmacol.

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INTRODUcrIONThe importance of species differences in drug metabolism in understand ing the mechanism of action of many drugs has become increasingly evi dent. Several reviews and articles on the overall topic of drug metabolism have covered aspects of it (1-17). In addition, discussion of species differ ences in drug metabolism formed an important segment of a recent sympo sium, the proceedings of which contain a number of very informative papers (18)(19)(20)(21)(22)(23)(24).It would appear that the increasing interest in the subject stems from the premise that improved understanding and broader knowledge of species differences in drug metabolism will greatly improve our abilities to predict the pharmacologic and toxic010gic properties of a given compound in man from experimental data obtained in animals. It should also be pointed out that such studies, even when only indirectly reIated to drug therapy, have yielded valuable new biochemical information of quite fundamental nature. Examples of this type concern acetyl CoA, the role of pyridine nucleotides in oxygen incorporation, mechanisms of enzyme adaptation, human genetics, phylogenetic and ontogenetic enzyme development, intracellular structure, organ and membrane function, and biosynthesis of vitamin C (25). The in creased interest is also probably correlated with recent technological adv ances that will possibly enable one to study the physiological disposition and metabolic fate of a compound in several species within a relatively short pe riod of time.If the above comments sound encouraging, they may also be unduly opti mistic, at least insofar as prediction is concerned. For example, Williams (19) stated that aromatic hydroxylation varies quantitatively and qualita tively in haphazard fashion among species, and that one can not, at present, draw definite conclusions about the relationship between drugs, species, and metabolic routes. Brodie (23) is equally discouraging in another sense, namely, the possibility of discovering an animal species, that, drug-metabo lism-wise, is greatly similar to man. It should be pointed out here, however, that very little work of this type has been done with the higher nonhuman primates, i.e., the chimpanzee, gorilla, and orang-utan. The reader should also beware of the catchall name "monkey"since in many papers it refers to 99 Annu. Rev. Pharmacol. 1970.10:99-118. Downloaded from www.annualreviews.org Access provided by University of New South Wales on 08/14/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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Section: Iuu Nesmentioning

confidence: 94%

Species Differences in Drug Metabolism

Hücker¹

1970

Annu. Rev. Pharmacol.

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“…22 These foundational studies inspired us to pursue a generalizable ‘dissection through vaccination’ method that could isolate the effects of single compounds within a structurally- and pharmacologically-diverse chemical system, such as that generated by fenethylline. 7–9 We termed the resulting approach “Determining the Identities of Species Supporting Expression of CNS-activity Through Incremental Vaccination”, or DISSECTIV (Extended Data Figure 1). …”

Section: Mainmentioning

confidence: 99%

“…5,6 These independently-active pharmacophores are liberated during metabolism, resulting in a structurally-diverse chemical mixture being deployed to the central nervous system. 7–9 Although fenethylline’s psychoactive properties have been reported to differ from other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. 10,11 Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate fenethylline’s psychoactivity and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine.…”

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confidence: 99%

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Wenthur

Zhou

Janda

2017

Nature

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SUMMARY PARAGRAPH Fenethylline, also known as Captagon, is a synthetic psychoactive stimulant that has recently been linked to substance use disorder and ‘pharmacoterrorism’ in the Middle East.1–4 Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it additionally incorporates a covalently-linked xanthine moiety into its parent structure.5,6 These independently-active pharmacophores are liberated during metabolism, resulting in a structurally-diverse chemical mixture being deployed to the central nervous system.7–9 Although fenethylline’s psychoactive properties have been reported to differ from other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects.10,11 Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate fenethylline’s psychoactivity and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacologic activity. We anticipate that DISSECTIV will be employed to expose unidentified active chemical species and illuminate pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples, and natural product extracts.

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“…Only a few studies have been performed concerning the metabolism of fenethylline in animals or human beings [12,[27][28][29][30].…”

Section: Metabolism Of Fenethyllinementioning

confidence: 99%

Fenethylline (Captagon) Abuse – Local Problems from an Old Drug Become Universal

Katselou

Papoutsis

Νικολάου

et al. 2016

Basic Clin Pharma Tox

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Fenethylline is a theophylline derivative of amphetamine having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon'. Unlike other drugs of abuse, the clandestine synthesis of fenethylline is simple, using inexpensive laboratory instrumentation and raw materials legal to obtain. A review of all the existing knowledge of fenethylline is reported, concerning its chemistry, synthesis, pharmacology and toxicology, legislation, its prevalence and use as drug of abuse, as well as its analysis in biological or seized samples. Published or reported captagon-related cases and seizures are also presented. All the reviewed information was gathered through a detailed search of PubMed and the Internet. The primary drug market for fenethylline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. In Arab countries, millions of captagon tablets are seized every year which represents one-third of global amphetamines seizures within a year. Furthermore, three of four patients treated for drug problems in Saudi Arabia are addicted to amphetamines, almost exclusively in the form of captagon. Significant information on fenethylline is provided for pharmacologists, toxicologists and forensic pathologists. Fenethylline, although old, has recently been introduced to the drug market, especially in Arab countries. Continuous community alertness is needed to tackle this current growing phenomenon.

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The metabolic fate of 3H-fenetylline in man

Cited by 39 publications

References 2 publications

Species Differences in Drug Metabolism

Species Differences in Drug Metabolism

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Fenethylline (Captagon) Abuse – Local Problems from an Old Drug Become Universal

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