McN5691  (Synonyms: RWJ26240)

McN5691 is a voltage-sensitive calcium channel blocker.

Calcium Channel^[1]

McN5691 (1 and 10 μM) prevents 60 mM KCl-induced contraction and calcium uptake and causes concentration-dependent relaxation (EC₅₀=190 μM) of 30 mM KCl-contracted aortic rings. At or below 10 μM, McN5691 (McN-5691) has no effects on basal tone or calcium uptake (45Ca) in isolated rings of rabbit thoracic aorta. McN5691 causes complete high affinity inhibition (K_d=39.5 nM) of specific diltiazem binding to the benzothiazepine receptor on the voltage-sensitive calcium channel in skeletal muscle microsomal membranes. In contrast to diltiazem, McN5691 inhibits specific dihydropyridine receptor binding, but the effect is biphasic with high (K_d=4.7 nM) and low (K_d=919.8 nM) affinity components. McN5691 inhibits norepinephrine (NE)-induced contraction (10 μM) and calcium uptake (1 and 10 μM) and causes concentration-dependent relaxation (EC₅₀=159 μM) of 1 μM NE-contracted rings of rabbit thoracic aorta^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

The excretion and metabolism of a 2-ethynylbenzenealkanamine analog, antihypertensive McN5691 (RWJ-26240), in beagle dogs is investigated. A total of 96.8% and 2.8% of the radioactive dose are excreted in feces and urine, respectively, during the 7 days after oral administration of ¹⁴C-McN5691. Of the radioactive dose, 96.8% and 2.8% is recovered in feces and urine, respectively, in the 7 days after oral administration of ¹⁴C-McN5691. More than 87% of the dose is excreted in feces during the 48 hours. McN5691 is extensively metabolized in dogs. Unchanged McN5691 is found in less than 0.1% and 19% of the dose in the 0-24 hour urine and 0-48 hour fecal extract, respectively, and 36% of the sample in the 4 hour plasma^[2]. In the McN5691 (McN-5691) study, vascular resistances tend to be higher in spontaneously hypertensive rat (SHR) than in Wistar-Kyoto (WKY) but the differences are statistically significant only in the cerebellum and the midbrain^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

457.60

C₃₀H₃₅NO₃

99254-95-2

COC1=C(OC)C=CC(CCN(C)C(C)CCC(C=C(OC)C=C2)=C2C#CC3=CC=CC=C3)=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Flaim SF, et al. Structurally novel antihypertensive compound, McN-5691, is a calcium channel blocker in vascular smooth muscle. J Pharmacol Exp Ther. 1991 Jan;256(1):279-88.  [Content Brief]

  [2]. Wu WN, et al. Excretion and metabolism of the antihypertensive agent, RWJ-26240 (McN-5691) in dogs. Drug Metab Dispos. 1998 Feb;26(2):115-25.  [Content Brief]

  [3]. Flaim SF, et al. Effects of the novel calcium channel blocker, McN-5691, on cardiocirculatory dynamics and cardiac output distribution in conscious spontaneously hypertensive rat. J Cardiovasc Pharmacol. 1988 Apr;11(4):489-500.  [Content Brief]