Celiprolol

Abstract

Celiprolol is a β-blocker with a unique pharmacologic profile: it is a β1-andrenoceptor antagonist with partial β2 agonist activity. Given this combination of effects, celiprolol may be better described as a selective adrenoreceptor modulator. It has antihypertensive and antianginal properties and is indicated for those uses in various countries around the world. In the United States, however, the proposed indication for this drug will be for the treatment of vascular type Ehlers–Danlos syndrome, a rare connective tissue disorder characterized by fragile arterial structure and an increased risk of life-threatening vascular complications. By reducing heart rate and pulsatile pressure, celiprolol may reduce the mechanical stress on collagen fibers within the arterial wall and be of benefit in patients with vascular type Ehlers–Danlos syndrome. The largest investigation of celiprolol in vascular Ehlers–Danlos syndrome was prematurely terminated due to significant benefit with celiprolol in reducing arterial events in patients with this condition. Celiprolol, therefore, represents a β-blocker that is unique from others in its class in both its pharmacology and clinical applications.

Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome

“…All findings from drug trials are based on analyses using a control group with n = 93 across all drug tests. FDR-adjusted P values are presented in Supplemental The fact that propranolol, a nonspecific β1/β2 antagonist, and atenolol, a specific β1 antagonist, had no impact on survival (Supplemental Figure 4), suggests the deleterious effect of celiprolol may be related to the drug's β2 agonism and/or α2 antagonism (38). ER stress and consequent autophagy due to abnormal collagen secretion has also been proposed as a possible pathogenic mechanism by which alterations in collagen III biosynthesis may lead to altered tissue mechanics and integrity (16,26).…”

A review of respiratory manifestations and their management in Ehlers-Danlos syndromes and hypermobility spectrum disorders

“…43 The mechanism of action is thought to be a result of increased vasodilation and production of type III collagen, reducing the risk of large arterial ruptures. 75,76 Additional management strategies include lifestyle changes to minimize risk of trauma, maintain good blood pressure control, and development of an individualized emergency treatment plan. Annual monitoring of the vascular tree utilizing ultrasound, CT-arteriography and nuclear magnetic resonance should be considered.…”

Vascular Ehlers-Danlos Syndrome with a Novel Missense Mutation in <i>COL3A1</i>: A Man in His 50s with Aortic Dissection after Interventional Treatment for Hemothorax as the First Manifestation

“…Blood pressure stabilization is the recommended treatment for patients with vascular EDS. In a randomized trial that was relatively large for a rare disease, celiprolol, a β1-adrenoceptor antagonist with β2-adrenoceptor agonist action, was shown to protect against severe vascular EDS complications, including cardiac and arterial events, by causing vasodilation or by boosting the production of type III collagen (16,17).…”