General pharmacological properties of the human corticotropin-releasing hormone corticorelin (human).
General pharmacological effects of the human corticotropin-releasing hormone, corticorelin (human) (CAS 86784-80-7), on the central nervous system, somatic nervous system, autonomic nervous system and smooth muscle, respiratory and circulatory system, digestive system and miscellaneous organs were investigated. 1. The central nervous system: Corticorelin (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 micrograms/kg i.v. induced flush of skin and pilo-erection, at doses of more than 30 micrograms/kg i.v. decreased body temperature, delayed expression of perphenazine-induced catalepsy and indicated hunched posture, and at the dose of 100 micrograms/kg i.v. induced the rise of awake-level and decrease of the total power of EEG, and decreased the spontaneous motor activity. 2. The somatic nervous system: Corticorelin (human) did not cause muscle relaxation in mice and had little effect on neuromuscular transmission in rats. No local anesthetic activity of corticorelin (human) was exhibited through inhibition of the corneal reflex in guinea pigs. 3. The autonomic nervous system and smooth muscle: Corticorelin (human) had no effect on the contraction of isolated ileum of guinea pigs induced by histamine and acetylcholine, and on the contraction of isolated trachea of guinea pigs induced by histamine, and the pupil diameter of rabbits. Corticorelin (human) at doses more than 30 micrograms/kg i.v. decreased spontaneous motility and contractile force of uterus of non-pregnant rabbits. 4. The respiratory and circulatory system: Corticorelin (human) had no effect on the contraction of isolated aorta of rats induced by norepinephrine. Corticorelin (human) at doses of more than 3 micrograms/kg i.v. decreased the blood pressure, increased heart rates and slightly increased the number of respiration in dogs. However, corticorelin (human) had no effect on ECG and femoral blood flow in dogs. 5. The digestive system: Corticorelin (human) at doses of more than 0.3 microgram/kg i.v. increased duodenal motility and contractile force, at doses of more than 1 microgram/kg i.v. increased colonic contractile force transiently and increased antral motility. Corticorelin (human) at doses of more than 3 micrograms/kg i.v. caused diarrhea and at doses of more than 30 micrograms/kg i.v. inhibited small intestinal propulsion in mice. Corticorelin (human) at dose of 100 micrograms/kg i.v. showed an inhibition of the gastric juice secretion and decreased the excretion of Na+, Cl- and H+ in rats. Corticorelin (human) produced slight gastric damages only at the highest dose of 100 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 400 WORDS)
Andoh
K
K
Pharmaceuticals Laboratory I, Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan.
Kimura
T
T
Saeki
I
I
Tabata
R
R
Yamazaki
S
S
Eguchi
I
I
Hanazuka
M
M
Horii
D
D
Munt
P L
PL
Davis
A S
AS
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000187:drug effects; D017933:Peripheral Nervous System / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012137:Respiratory System / Q000187:drug effects
D003346:Corticotropin-Releasing Hormone