(-)-Perhexiline

277.5 g/mol

277.49

252-426-3|229-569-5|254-558-7|254-559-2

DTXSID7023439

C - Cardiovascular system

12 Ų

6.2

2.72e-05 g/L

Oral LD50 rat: 2150 mg/kg; Oral LD50 Mouse: 2641 mg/kg. Short term adverse effects include nausea, transient dizziness, hypoglycaemia in diabetic patients, and torsade de pointes (rare).

Perhexiline and its metabolites are highly protein bound (>90%).

For the management of severe angina pectoris.

Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures.

Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)|A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (See all compounds classified as Calcium Channel Blockers.)|Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. (See all compounds classified as Cardiovascular Agents.)

Well absorbed (>80%) from the gastrointestinal tract following oral administration.

The principal metabolites of perhexiline in man are monohydroxyperhexiline (which is excreted, in part, conjugated with glucuronic acid) and dihydroxyperhexiline that accounts for a relatively small proportion of the total metabolites. Two unidentified metabolites have also been found in the faeces. The pharmacological activity of the metabolites is not known. Hydroxylation of perhexiline is controlled by cytochrome P450 2D6 (CY P450 2D6).

Variable and non-linear. Some reports show a half-life of 2-6 days, others indicate it could be as high as 30 days.

Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1 and CPT-2. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT-1 and, to a lesser extent, CPT-2, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O2 consumption as before and consequently increases myocardial efficiency.

Perhexilene