Tryptoline, also known as tetrahydro-β-carboline and tetrahydronorharmane, is a natural organic derivative of ''beta''-carboline. It is an

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

chemically related to

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

s. Derivatives of tryptoline have a variety of pharmacological properties and are known collectively as tryptolines.

Pharmacology

Many tryptolines are competitive selective inhibitors of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...

type A (

MAO-A Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, s ...

). 5-Hydroxytryptoline and 5-methoxytryptoline (pinoline) are the most active

monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...

(MAOIs) with IC₅₀s of 0.5 μM and 1.5 μM respectively, using 5-hydroxytryptamine (serotonin) as substrate. Tryptolines are also potent

reuptake inhibitor Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmit ...

s of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

, with a significantly greater selectivity for serotonin. Comparison of the inhibition kinetics of tetrahydro-β-carbolines for serotonin and epinephrine reuptake to that of the platelet aggregation response to these amines has shown that 5-hydroxymethtryptoline, methtryptoline, and tryptoline are poor inhibitors of reuptake. In all respects 5-hydroxytryptoline and 5-methoxytryptoline showed greater pharmacological activity than the tryptoline and methtryptoline. Although the ''in vivo'' formation of tryptolines has been a matter of controversy, they have profound pharmacological activity.

References

* {{cite journal , author1 =H. Rommelspacher , author2 =H. Kauffmann , author3 =C. Heyck Cohnitz , author4 = H. Coper , title =Pharmacological properties of tetrahydronorharmane (Tryptoline) , journal =Journal Naunyn-Schmiedeberg's Archives of Pharmacology , year =1977 , volume =298 , issue =2 , pages =83–91 , doi =10.1007/BF00508615 Tryptamine alkaloids Beta-Carbolines Monoamine oxidase inhibitors

Pharmacology

See also

References