A benzamide-sulfonamide-indole. It is called a thiazide-like diuretic but structure is different enough (lacking the thiazo-ring) so it is not clear that the mechanism is comparable. [PubChem]
Indication
For the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). Also used for the management of edema as a result of various causes.
Pharmacology
Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide bears a structural similarity to the triazide diuretics which are known to decrease vascular smooth muscle reactivity. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. This same effect may cause hypokalcemia in susceptible individuals. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. Overall, indapamide has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.
Toxicity
Side effects include electrolyte imbalance (potassium or salt depletion due to too much fluid loss), nausea, stomach disorders, vomiting, weakness
Affected Organisms
Humans and other mammals
Biotransformation
Primarily hepatic. Indapamide is an extensively metabolized drug with only about 7+ACU- of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
Absorption
Rapidly absorbed from gastrointestinal tract.
Half Life
14 hours (biphasic)
Protein Binding
71-79%
Elimination
Indapamide is an extensively metabolized drug, with only about 7% of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
References
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Dong DL, Wang QH, Yue P, Jiao JD, Gu RM, Yang BF: Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84. Epub 2006 Mar 2.
[Pubmed]
Research Area: Cardiovascular Disease Biological Activity: Indapamide(Lozol) is a non-thiazide sulphonamide diuretic compound, generally used in the treatment of hypertension, as well as decompensated cardiac failure. Indapamide (Lozol) helps prevent your body from absorbing too much salt, which can cause fluid retention. Indapamide (Lozol) treats fluid retention (edema) in people with congestive heart failure. [1]
Other Notes Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. I1887.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.
