Chemical formula: C₁₃₆H₂₁₀N₄₀O₃₁S Molecular mass: 2,933.49 g/mol PubChem compound: 16133751
Tetracosactide acetate consists of the first 24 amino acids occurring in the natural corticotropic hormone (ACTH) sequence and displays the same physiological properties as ACTH. In the adrenal cortex, it stimulates the biosynthesis of glucocorticoids, mineralocorticoids, and, to a lesser extent, androgens, which explains its therapeutic effect in conditions responsive to glucocorticoid treatment.
However, its pharmacological activity is not comparable to that of corticosteroids, because under ACTH treatment (in contrast to treatment with a single glucocorticoid) the tissues are exposed to a physiological spectrum of corticosteroids. Increasing doses of tetracosactide does not increase the pharmacodynamic response, however increases the duration of action. Prolonged use of tetracosactide is reported to have minimal suppression of hypothalamic-pituitary-adrenal axis as compared to long-term corticosteroids.
The site of action of ACTH is the plasma membrane of the adrenocortical cells, where it binds to a specific receptor. The hormone-receptor complex activates adenylate cyclase, stimulating the production of cyclic AMP (adenosine monophosphate) and so promoting the synthesis of pregnenolone from cholesterol. From pregnenolone the various corticosteroids are produced via different enzymatic pathways.
After 1 mg of tetracosactide i.m., the cortisol levels increases and the highest values are recorded during the first 8 to 12 hours after the injection. The increased cortisol levels are maintained up to 24 h and return to basal levels after around 36-48 h.
Tetracosactide acetate is absorbed on to a zinc phosphate complex which ensures the sustained release of the active substance from the intramuscular injection site. After an intramuscular injection of 1mg tetracosactide, the radioimmunologically determined plasma concentrations of tetracosactide acetate range between 200 to 300pg/ml and are maintained for 12 hours.
Tetracosactide is rapidly distributed and concentrated in the adrenals and kidneys, which lead to rapid decrease in its plasma levels.
There is no evidence of binding of ACTH to any particular plasma protein, though some non-specific interaction with albumin has been reported. Tetracosactide acetate has an apparent volume of distribution of approximately 0.4litres/kg.
In the serum, tetracosactide acetate is broken down by serum endopeptidases into inactive oligopeptides and then by aminopeptidases into free amino acids. Its rapid elimination from plasma is probably attributable not so much to this relatively slow process as to the fact that the active substance is rapidly concentrated in the adrenals and kidneys.
Following an intravenous dose of 131I-labelled tetracosactide acetate, 95 to 100% of the radioactivity is excreted in the urine within 24 hours.
No studies have been performed to evaluate the mutagenic or carcinogenic potential of tetracosactide. No animal studies on fertility and reproduction toxicity have been performed with tetracosactide.
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