Benzodiazepines naturally occurring

Huen MSY, Kwok-Min H, Leung JWC, Sigel E, Baur R, Wong JTF. Naturally occurring 2 -hydroxyl-substituted flavonoids as high-affinity benzodiazepine site ligands. Biochem Pharmacol 2003 66 2397-2407. 

Meier B. (1995). Passiflora incarnata L.—Passion flower. Zeitschrift fur Phytotherapie. 16(2) 115-26. Medina JH, Paladini AC, Wolfman C, Levi de Stein M, Calvo D, Diaz LE, Pena C. (1990). Chrysin (5,7-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties. Biochem Pharmacol. 40(10) 2227-31. 

Nielsen M, Frokjaer S, Braestrup C. (1988). High affinity of the naturally-occurring biflavonoid, amentoflavon, to brain benzodiazepine receptors in vitro. Biochem Pharmacol. 37(17) 3285-87. 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

The C(2)-C(3) olefin of a l,4-benzodiazepin-5-one regiospecifically captured an alkyl radical intramolecularly in a 5-f vo-/r/g-proccss that is the critical step in an approach to the constmction of the fused tricyclic system found in the pyrrolo[2,l-f][l,4]benzodiazepine class of antitumor antibiotic. Treatment of the alkyl bromide 46 with Bu3SnH afforded the tricyclic product 47 in 90% yield, a reaction that proceeded with equal efficiency with the alkoxy aryl ring substituents found in the naturally occurring ( )DC-81 (Scheme 18) <19990L1835>. 

While there are no newly reported naturally occurring benzodiazepines since the first survey (7 ). the interest in this area remains high. The current status of research and clinical implications has been reviewed (1484). It is noted that natural benzodiazepines, including seven known halogenated examples (1), are found in soil, plants, animal and human tissues, and are chemically identical to their pharmaceutical counterparts. The endogenous formation of benzodiazepines by plant cells (Artemisia dracunculus and Solarium tuberosum) has been demonstrated for delor-azepam, temazepam, and diazepam (1485). 

Sand P, Kavvadias D, Feineis D, Riederer P, Schreier P, Kleinschnitz M, Czygan F-C, Abou-Mandour A, Bringmann G, Beckmann H (2000) Naturally Occurring Benzodiazepines Current Status of Research and Clinical Implications. Eur Arch Psychiatry Clin Neurosci 250 194... 

The third group of compounds are the naturally occurring benzodiazepines. Desmethyldiazepam has been isolated from human brains which were stored frozen in the 1930s, at least two decades before the benzodiazepines were developed. While there is no evidence that the benzodiazepine structure can be synthesized enzymatically in the mammalian brain, several other compounds of this type have since been isolated from cattle brain and from human breast milk. One possibility is that gastrointestinal flora can partially synthesize the benzodiazepine molecule and it is also known that plants such as wheat and potatoes are a potential source of diazepam, desmethyldiazepam and lormetazepam. If it is eventually shown that the local brain concentration of these benzodiazepines is sufficiently high to activate the benzodiazepine receptors then the possibility arises that anxiety disorders could result from a lack of these endozepines. 

In SUMMARY, the naturally occurring ligands for the benzodiazepine and /or GABA-A receptor sites that act as sedative-hypnotics or anxiolytics all directly or indirectly augment GABA-A receptors and thereby depress neuronal activity. In this respect they act in a similar way to the various classes of drugs used to treat anxiety and insomnia. Such compounds do not induce natural sleep. They all increase slow-wave sleep but reduce REM sleep. 

Izquierdo, I. and Medina, J. (Eds) Naturally Occurring Benzodiazepines. New York Ellis Horwood, 1993. 

VII. Biological Activity of Naturally Occurring Benzodiazepine Alkaloids. 93... 

The first correct structures of benzodiazepine alkaloids, namely, those of cyclopenin (3) and cyclopenol (4), were published in 1963 by Mohammed and Luckner (47). In 1965 the structure of the antibiotic anthramycin (8) was established (28), followed by tomaymycin (12) and oxotomaymycin (13) in 1971 (26). The biosynthetic pathway to both the cyclopenin group and the anthramycin-tomaymycin group of alkaloids was elucidated in the following years and has been included in previous reviews (32,33). Later additions to the small list of naturally occurring benzodiazepines comprise aszonalenin (6) (16), asperlicin (7) (31), and auranthine (5) (85). The biosynthesis of the latter alkaloids has not yet been investigated in detail. 

Fig. 1. Overview of the structures of naturally occurring benzodiazepine alkaloids (see Table I for references).

All naturally occurring benzodiazepines are biosynthesized from anthranilic acid. The benzodiazepine moiety is formed by reacting this central precursor with derivatives of phenylalanine (cyclopenin group), tyrosine (tomaymycin-anthramycin group), glutamine (auranthine), or tryptophan plus another molecule of anthranilic acid (asperlicin). Intensive biosynthetic work has been published for the cyclopenin and tomaymycin-anthramycin groups only. 

Izquierdo Medina NATURALLY OCCURRING BENZODIAZEPINES Structure, Distribution and Function... 

In any case, the darkening reaction doesn t pose a health hazard. Even if your potatoes have turned black, you can still eat them. After all, potatoes are a true comfort food. Due to their high carbohydrate content, they elevate serotonin levels in the brain, which has a calming effect. And, believe it or not, researchers have discovered that potatoes harbor small amounts of naturally occurring benzodiazepines, compounds in the same chemical family as Valium. So, go ahead and enjoy your Christmas pudding, white or black. 

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