GENERAL PHARMACOLOGICAL PROPERTIES OF THE HUMAN CORTICOTROPIN-RELEASING HORMONE CORTICORELIN (HUMAN)

General pharmacological effects of the human corticotropin-releasing h ormone, corticorelin (human) (CAS 86784-80-7), on the central nervous system, somatic nervous system, autonomic nervous system and smooth mu scle, respiratory and circulatory system, digestive system and miscell aneous organs were investigated 1. The central nervous system: Cortico relin (human) had little effect on hexobarbital-induced sleeping-time, maximal electroshock-induced convulsion, acetic acid-induced writhing , rota-rod performance. Corticorelin (human) at doses of more than 10 mu g/kg i.v. induced flush of skin and pilo-erection, at doses of more than 30 mu g/kg i.v. decreased body temperature, delayed expression o f perphenazine-induced catalepsy and indicated hunched posture and at the dose of 100 mu g/kg i.v. induced the rise of awake-level and decre ase of the total power of EEG, and decreased the spontaneous motor act ivity 2. The somatic nervous system:. Corticorelin (human) did not cau se muscle relaxation in mice and had little effect on neuromuscular tr ansmission in rats. No local anesthetic activity of corticorelin (huma n) was exhibited through inhibition of the corneal reflex in guinea pi gs. 3. The autonomic nervous system and smooth muscle: Corticorelin (h uman) had no effect on the contraction of isolated ileum of guinea pig s induced by histamine and acetylcholine, and on the contraction of is olated trachea of guinea pigs induced by histamine, and the pupil diam eter of rabbits. Corticorelin (human) at doses more than 30 mu g/kg i. v. decreased spontaneous motility and contractile force of uterus of n on-pregnant rabbits. 4. The respiratory and circulatory system: Cortic orelin (human) had no effect on the contraction of isolated aorta of r ats induced by norepinephrine. Corticorelin (human) at doses of more t han 3 mu g/kg i.v. decreased the blood pressure, increased heart rates and slightly increased the number of respiration in dogs. However, co rticorelin (human) had no effect on ECG and femoral blood flow in dogs . 5. The digestive system: Corticorelin (human) at doses of mole than 0.3 mu g/kg i.v. increased duodenal motility and contractile force, at doses of more than 1 mu g/kg i.v. increased colonic contractile force transiently and increased antral mortility. Corticorelin (human) at d oses of mole than 3 mu g/kg i.v. caused diarrhea and at doses of more than 30 mu g/kg i.v. inhibited small intestinal propulsion in mice. Co rticorelin (human) at dose of 100 mu g/kg i.v. showed an inhibition of the gastric juice secretion and decreased the excretion of Na+, Cl- a nd H+ in rats. Corticorelin (human) produced slight gastric damages on ly at the highest close of 100 mu g/kg i.v. 6. Other properties: Corti corelin (human) had no effect on the carrageenan-induced edema formati on and on the blood coagulation process and did not show hemolytic eff ects. Corticorelin (human) at doses of more than 3 mu g/kg increased t he excretion of urinary K+. Corticorelin (human) at doses of more than 30 mu g/kg i.v. increased the plasma glucose level. The results show that corticorelin (human) has little effect on the central nervous sys tem, the somatic nervous system, the autonomic nervous system and smoo th muscle except on the respiratory and circulatory system and the dig estive system. Because all of the effects are weak and observed at rel atively high doses, it is suggested that corticorelin (human) is accep table in clinical use.