Indole Alkaloids - Physiological Activity

Physiological Activity

Indole alkaloids act on the central and peripheral nervous systems. Besides, bisindole alkaloids vinblastine and vincristine show antineoplastic effect.

Because of structural similarities with serotonin, many tryptamines can interact with serotonin 5-HT receptors. The main effect of the serotonergic psychedelics such as LSD, DMT, and psilocybin is related to them being agonists of the 5-HT_2A receptors. In contrast, gramine is an antagonist of the 5-HT_2A receptor.

Ergolines, such as lysergic acid, include structural elements of both tryptamine and phenylethylamine and thus act on the whole group of the 5-HT receptors, adrenoceptors (mostly of type α) and dopamine receptors (mostly type D₂). So ergotamine is a partial agonist of α-adrenergic and 5-HT₂ receptors, and thus narrows blood vessels and stimulates constriction of the uterus. Dihydroergotamine is more selective to α-adrenergic receptors and has a weaker effect on serotonin receptors. Ergometrine is an agonist of α-adrenergic, 5-HT₂ and partly D₂ receptors. Compared with other ergot alkaloids, ergometrine has a greater selectivity in stimulating the uterus. LSD, a semi-synthetic psychedelic ergoline, is an agonist of 5-HT_2A, 5-HT_1A and to a lesser extent D₂ receptors and has a powerful psychedelic effect.

Some monoterpenoid indole alkaloids also interact with adrenoceptors. For example, ajmalicine is a selective antagonist of α₁-adrenergic receptors and therefore has antihypertensive action. Yohimbine is more selective to α₂ adrenoceptor; by blocking presynaptic α₂-adrenoceptors, it increases the release of norepinephrine thereby raising the blood pressure. Yohimbine was used for the treatment of erectile dysfunction in men until emergence of more efficient drugs.

Some alkaloids affect the turnover of monoamines indirectly. So, harmine and harmaline are reversible selective inhibitors of monoamine oxidase-A. Reserpine reduces concentration of monoamines in presynaptic and synaptic neurons, thereby inducing antihypertensive and antipsychotic effects.

Some indole alkaloids interact with other types of receptors. Mitragynine is an agonist of the μ-opioid receptor. Harmal alkaloids are antagonists to the GABA_A-receptor, and ibogaine – to NMDA-receptors. Physostigmine is a reversible acetylcholinesterase inhibitor.