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JNJ-39588146

Johnson & Johnson

Drug Names(s): stresscopin

Description: JNJ-39588146 is a synthetic acetate salt of human stresscopin, a ligand for the type 2 corticotropin-releasing hormone receptor (CRHR2). Stresscopin has ~38% homology with urocortin II and ~20% homology with urocortin I.

Stresscopin is found in a variety of tissues, including brain, gastrointestinal tract, pancreatic islets, skin, heart and kidney. Its receptor is also found in the adrenal glands. The receptor (CRHR2) is also targeted by urocortin II.

Preclinically, administration into the central nervous system increases blood pressure and plasma catecholamines. However, in a sheep model of heart failure, peripheral administration led to reduced peripheral resistance, improved cardiac output, reduced neurohormonal activation (though ACTH and cortisol were increased; it's not clear if this would occur in humans), and improved renal function. Blood pressure was increased in normal sheep (as was heart rate) but reduced in heart failure (heart rate not reported). Comparing preclinical studies, the onset of action appears faster and the duration of action shorter than urocortin I or II. Stresscopin, like urocortin II, also has cardioprotective effects in ischemia/reperfusion injury. One preclinical study of urocortin II, however, found that increased inotropy was accompanied by arrhythmogenesis (also seen in human heart tissue), so this could be of concern for stresscopin, as well.

Other preclinical findings include suppression of food intake, delay in gastric emptying and decreases in heat-induced edema.


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