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
BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Th ...
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 substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
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 fir ...
type A (
MAO-A). 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
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (locomotion), the surface over which an organism lo ...
.
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 transmitt ...
s of
serotonin 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.
See also
*
Norharmane
*
harmane
*
beta-Carboline
*
Harmala alkaloid
Several alkaloids that function as monoamine oxidase inhibitors (MAOIs) are found in the seeds of '' Peganum harmala'' (also known as '' Harmal'' or ''Syrian Rue''), as well as tobacco leaves including harmine, harmaline, and harmalol, which a ...
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