Trichlormethiazide

Trichlormethiazide

Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	B (D if used to treat pregnancy-induced hypertension)
Routes of administration	Oral (capsules, tablets, oral solution)
ATC code	C03AA06 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Variably absorbed from GI tract
Excretion	Primarily excreted unchanged in urine
Identifiers
IUPAC name 6-Chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2H-benzo[e] [1,2,4]thiadiazine-7-sulfonamide
CAS Number	133-67-5^Y
PubChem CID	5560
IUPHAR/BPS	7314
DrugBank	DB01021^N
ChemSpider	5359^N
UNII	Q58C92TUN0
KEGG	D00658^N
ChEMBL	ChEMBL1054^N
CompTox Dashboard (EPA)	DTXSID7023699
ECHA InfoCard	100.004.654
Chemical and physical data
Formula	C8H8Cl3N3O4S2
Molar mass	380.64 g·mol^−1
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Trichlormethiazide (INN, currently being sold under the brand names of Achletin, Diu-Hydrin and Triflumen) is a diuretic with properties similar to those of hydrochlorothiazide.^[1] It is usually administered for the treatment of oedema (including that which is associated with heart failure, hepatic cirrhosis and corticosteroid therapy) and hypertension.^[1] In veterinary medicine, trichlormethiazide can be combined with dexamethasone to be used on horses with mild swelling of distal limbs and general bruising.^[2]

As a diuretic (in particular a thiazide), trichlormethiazide encourages water loss from the body.^[1] Trichlormethiazide works by inhibiting Na⁺/Cl⁻ ion reabsorption from the distal tubules of the kidneys.^[1] In addition, trichlormethiazide increases the excretion of potassium.^[1]

Mechanism

Trichlormethiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle. This results in excretion of sodium, chloride and water, and thus acts as a diuretic.^[1] Although trichlormethiazide is used to treat hypertension, its hypotensive effects may not necessarily be due to its role as a diuretic.^[1] Thiazides in general cause vasodilation by activating calcium-activated potassium channels in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.^[1]

Synthesis

Trichlormethiazide synthesis:^{[3][4][5][6][7][8]}

References

1. "DrugBank: DB01021 (Trichlormethiazide)". DrugBank. Retrieved 2008-01-23.
2. "Trichlormethiazide and Dexamethasone for veterinary use". Wedgewood Pharmacy. Retrieved 2008-01-24.
3. GB 949373, "Benzthiadiazine derivatives and processes for their manufacture", published 1960, assigned to Scherico Ltd. 
4. DE 1147233, de Stevens G, Werner LH, "Verfahren zur Herstellung von 2-Alkenyl-7-sulfamyl-3, 4-dihydro-1, 2, 4-benzothiadiazin-1, 1-dioxyden", published 1960, assigned to Ciba Geigy 
5. De Stevens G, Werner LH, Barrett WE, Chart JJ, Renzi AH (March 1960). "The chemistry and pharmacology of hydrotrichlorothiazide". Experientia. 16 (3): 113–4. doi:10.1007/bf02158094. PMID 13815073. S2CID 35063235.
6. Sherlock MH, Sperber N, Topliss J (May 1960). "3-Haloalkyl-dihydrobenzothiadiazine dioxides as potent diuretic agents". Experientia. 16 (5): 184–5. doi:10.1007/BF02178974. S2CID 3086415.
7. GB 954023, "Novel process for preparation of dihydrobenzothiadiazines", published 1960, assigned to Scherico Ltd. 
8. US 3264292, Close WJ, published 1960, assigned to Abbott Labs