EXP-3174

Overview

EXP-3174 is a pharmacologically active metabolite of the angiotensin II receptor antagonist Losartan. It is primarily known for its role in the treatment of hypertension and certain types of heart failure. EXP-3174 is a potent non-peptide compound that contributes significantly to the therapeutic effects of Losartan by blocking the action of angiotensin II, a hormone that causes blood vessels to constrict.

Chemical Structure and Properties

EXP-3174 is chemically classified as a carboxylic acid metabolite of Losartan. Its molecular formula is C22H22ClKN6O2, and it has a molecular weight of approximately 461.01 g/mol. The compound is characterized by its high affinity for the angiotensin II type 1 (AT1) receptor, which is crucial for its antihypertensive effects.

Mechanism of Action

The primary mechanism of action of EXP-3174 involves the selective inhibition of the AT1 receptor. By blocking this receptor, EXP-3174 prevents angiotensin II from binding, thereby inhibiting its vasoconstrictive and aldosterone-secreting effects. This leads to vasodilation, reduced blood pressure, and decreased workload on the heart.

Pharmacokinetics

EXP-3174 is formed in the liver through the oxidation of Losartan by the cytochrome P450 enzyme system, particularly CYP2C9 and CYP3A4. It has a longer half-life than Losartan, which contributes to its prolonged antihypertensive effects. The metabolite is primarily excreted in the urine and feces.

Clinical Significance

The presence of EXP-3174 enhances the efficacy of Losartan in managing hypertension and heart failure. Its ability to maintain blood pressure control over a 24-hour period makes it a valuable component of Losartan therapy. Additionally, EXP-3174 has been studied for its potential renal protective effects, particularly in patients with type 2 diabetes and nephropathy.

Research and Development

Ongoing research is focused on understanding the broader implications of EXP-3174 in cardiovascular and renal health. Studies are exploring its role in reducing proteinuria and slowing the progression of kidney disease in diabetic patients.

Safety and Side Effects

As a metabolite of Losartan, EXP-3174 shares a similar safety profile. Common side effects include dizziness, headache, and fatigue. Rare but serious side effects may include hyperkalemia and renal impairment, particularly in patients with pre-existing kidney conditions.

Also see

• Losartan
• Angiotensin II receptor antagonist
• Hypertension
• Heart failure
• Pharmacokinetics