Introduction

The pineal indole, namely 5-methoxytryptamine(5-MT; Figure 1), one of the biogenic monoamines, would play antitumor effects, by either inhibiting cancer cell proliferation or stimulating the anticancer immunity.[1] 5-Methoxytryptamine has been shown to exert several interesting and possibly important pharmacological actions including contraction of smooth muscle. cardiovascular effects, respiratory depression, a hypocalcemic effect, and a possible protecting action against the toxic effects of whole body irradiation. Within the CNS, 5-methoxytryptamine has been reported to alter EEG patterns, to mimic the actions of 5-HT on brainstem neurons, and to stimulate neonate 5-HT-sensitive adenyl cyclase. Behavioral effects of 5-methoxytryptamine include disruption of the conditioned avoidance response and rope climbing performance in rats, along with a possible hyperkinetic syndrome. Intraventricular administration of 5-methoxytryptamine has been shown to produce a catatonic state in rats.[2]

5-Methoxytryptamine biosynthesis

The way of 5-MT synthesis, via a deacetylation of melatonin (MEL), also exists. This possibility first was suggested by the observations of Kopin et al. and Kveder &Mclsaac on the metabolism of MEL in whole animals. In these studies, following MEL administration a small amount of 5-methoxyindole acetic acid (5-MIAA), the deamination product of 5-MT, was found in the the urine. Kveder & Mclsaac hypothesized that this metabolite was derived from 5-MT formed as a result of the deacetylation of MEL. Rogawski et al. first demonstrated the existence of this phenomenon, observing that incubation of liver slices in vitro with tritiated MEL led tothe formation of tritiated 5-MT. This result was confirmed in vitro as well as in vivo by Beck & Jonsson. MEL (0.2-2%) was converted to 5-MT by the action of liver arylacylamidase. Beck & Jonsson also demonstrated that neither the pineal nor the brain were able, at least not in in vitro conditions, to convert MEL into 5-MT. The possible amount of 5-MT formed in such a way compared to that formed via O-methylation of serotonin suggests that the peripheral deacetylation of MEL is a minorsynthetic pathway, occurring primarily in the liver and perhaps also in the kidney. However, this does not mean that this process is not of physiological importance. For example, Beck & Jonsson observed in intact rats an increase in pineal 5-MT concentration after injection of large doses of MEL.[3] 

The physiological distribution of endogenous 5-Methoxytryptamine 

Distribution of 5-methoxytryptamine in the periphery seems to parallel that of 5-HT with highest levels being found in the GI tract and Harderian gland. Smaller quantities were detected in the lung, spleen, kidney, plasma and heart, while no 5-HT was detected in the adrenals. testes or skeletal muscle.The regional distribution of 5-methoxytryptamine in the CNS of the rat did not always parallel that of 5-HT. Although 5-methoxytryptamine levels were highest in the pineal gland, where 5-HT is abundant, and lowest in the cerebellum,where 5-HT is also low, certain other areas did not follow this pattern. For example, 5-methoxytryptamine levels are low in the midbrain where 5-HT levels are high, while in the striatum 5-methoxytryptamine is high whereas 5-HT levels are low. Relatively large amounts of 5-methoxytryptamine were found in the brainstem, thalamus, and hypothalamus,regions known to be rich in 5-HT. Pretreatment of rats with iproniazid resulted in a 50% increase in whole brain 5-methoxytryptamine (P < 0.05 as determined by a paired t-test) while reserpine pretreatment had little effect.

Whole brain levels of 5-methoxytryptamine in the rat were found to be relatively stable after death with only a slight decrease after 13 h being noted.5-Methoxytryptamine was detected in the CNS of all species examined. No marked interspecies differences were observed. 5-Methoxytryptamine was found in the hypothalamus,brainstem and pineal of all species, in the striatum and thalamus of all species except the dog, and in the hippocampus of the dog and baboon. Although 5-methoxytryptamine was detected in the cerebral cortex of the baboon, it was not detected in this region in any of the other species. Areas of special interest include the baboon medulla where 5-methoxytryptamine is very abundant and the human pineal where levels are comparatively low.

Certain human fluids were found to contain measurable quantities of 5-methoxytryptamine. Using pooled human CSF samples from 7 to 10 individuals, researchers found 5-methoxytryptamine to be present at a level of 1.5±0.5 ng/ml (N=2). Although researchers were unable to detect 5-methoxytryptamine in portions of plasma (l0-20ml) from five different subjects, measurable amounts were found in the urine of all five subjects tested. Average nightly excretion (12:00-8:00a.m.) was found to be 204±108ng with a mean concentration of 0.5 ng/ml.[2] 

References

[1]Bayari S, Ide S. Fourier transform infrared spectra and molecular structure of 5-methoxytryptamine, N-acetyl-5-methoxytryptamine and N-phenylsulfonamide-5-methoxytryptamine. Spectrochim Acta A Mol Biomol Spectrosc. 2003;59(6):1255-1263. doi:10.1016/s1386-1425(02)00308-6.

[2]Prozialeck WC, Boehme DH, Vogel WH. The fluorometric determination of 5-methoxytryptamine in mammalian tissues and fluids. J Neurochem. 1978;30(6):1471-1477. doi:10.1111/j.1471-4159.1978.tb10480.x

[3]Pévet P. Is 5-methoxytryptamine a pineal hormone?. Psychoneuroendocrinology. 1983;8(1):61-73. doi:10.1016/0306-4530(83)90041-0