Incyclinide (proposed trade name Metastat) is a chemically modified
tetracycline antibiotic
Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. ...
that was investigated in clinical trials for the treatment of
rosacea
Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, en ...
,
various tumours, allergic and inflammatory diseases and a number of other conditions.
Data from animal studies suggest that centrally infused incyclinide attenuates
microglia
Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...
l mediated neuroinflammation in the
paraventricular nucleus
The paraventricular nucleus (PVN) is a nucleus in the hypothalamus, located next to the third ventricle. Many of its neurons project to the posterior pituitary where they secrete oxytocin, and a smaller amount of vasopressin. Other secretions ...
of the
hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
and sympathetic activation in
angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the ...
-induced hypertension. This was also associated with unique changes in gut microbial communities and profound attenuation of gut pathology in animal models of hypertension.
Mechanism of action
Like other tetracyclines, incyclinide inhibits
matrix metalloproteinases
Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...
. In contrast to traditional tetracyclines, it lacks antibiotic properties.
References
{{antibiotic-stub
Tetracycline antibiotics