January 1, 2006Drug and Chemical Toxicology

The First Preclinical Pharmacotoxicological Safety Assessment of CGS 35601, a Triple Vasopeptidase Inhibitor, in Chronically Instrumented, Conscious, and Unrestrained Spontaneously Hypertensive Rats

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Why the study?

Does CGS 35601 safely reduce blood pressure in spontaneously hypertensive rats?

Population

Chronically instrumented, unrestrained, conscious, male, spontaneously hypertensive rats (SHR) (n=23 to 28)

Comparison

CGS 35601 at escalating doses of 0.01, 0.1, 1… vs Vehicle via continuous intra-arterial infusion

Design

Preclinical

Follow-up

20 days

Authors

PDPhilippe DaullSanten (France)RLRaymond LepageUniversité de Sherbrooke OBOuhida BenrezzakUniversité de Sherbrooke

Discussion

Member takes

Implication

Does not support clinical use; leaves open translation of triple vasopeptidase inhibition to human hypertension trials.

Structured PICO

Does CGS 35601 safely reduce blood pressure in spontaneously hypertensive rats?

Population

Chronically instrumented, unrestrained, conscious, male, spontaneously hypertensive rats (SHR) (n=23 to 28)

Intervention

CGS 35601 (triple vasopeptidase inhibitor) at escalating doses of 0.01, 0.1, 1 and 5 mg/kg/day via continuous intra-arterial infusion for 5 consecutive days per dose, followed by a 5-day washout

Comparator

Vehicle (saline) via continuous intra-arterial infusion

Outcome

Safety profile and toxicity (assessed via daily hemodynamics, biochemical and hematological measurements, growth, diuresis, and renal/hepatic activity)safety

CGS 35601, a novel triple vasopeptidase inhibitor, effectively lowers blood pressure without acute safety or toxicity concerns in a preclinical hypertensive rat model.

Limitations

Long-term chronic experiments are needed to assess possible angioedema and increases in vascular permeability.

Cite This Study

Daull et al. (2006) studied this question.

synapsesocial.com/papers/6a744953c2eb6969bf0930ab https://doi.org/10.1080/01480540600566717

Topics

Hypertension management

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The First Preclinical Pharmacotoxicological Safety Assessment of CGS 35601, a Triple Vasopeptidase Inhibitor, in Chronically Instrumented, Conscious, and Unrestrained Spontaneously Hypertensive Rats

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Topics

The First Preclinical Pharmacotoxicological Safety Assessment of CGS 35601, a Triple Vasopeptidase Inhibitor, in Chronically Instrumented, Conscious, and Unrestrained Spontaneously Hypertensive Rats

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Topics

Also Consider