General pharmacological profiles of the new beta-adrenoceptor antagonist carvedilol.
General pharmacological properties of carvedilol (BM 14.190) were investigated in comparison with propranolol. 1. Central nervous system: Carvedilol caused reduction of awareness, motor activity and muscle tone, and staggering gait in Irwin's test (mice). It decreased spontaneous motor activity and potentiated hexobarbital anesthesia (mice). It lacked anticonvulsant activity (mice) and did not have any effect on body temperature (rabbits). Various changes were produced in mono- and polysynaptic spinal reflex (cats). In EEG, a slight arousal pattern was observed (cats). These effects of carvedilol were weaker than those observed after propranolol administration in general. Carvedilol, however, caused potentiation of hexobarbital anesthesia at lower doses than propranolol. Carvedilol inhibited acetic acid-induced writhing syndrome, whereas it failed to show analgesic activity in the tail-pinch test (mice). Propranolol inhibited both pain reactions. 2. Respiratory and cardiovascular system (dogs): Carvedilol increased respiratory rate and decreased expiratory velocity. It produced hypotension and bradycardia. Cardiac contractility was reduced and femoral blood flow was transiently increased after carvedilol administration. Propranolol induced weaker hypotension and greater bradycardia in comparison with carvedilol. It decreased femoral blood flow. 3. Autonomic nervous system: Carvedilol had little or no effects on pupil size, whereas propranolol produced mydriasis (rabbits). Carvedilol inhibited pressor response to norepinephrine (rats), and it also reduced the nictitating membrane contraction induced by pre- and postganglionic sympathetic nerve stimulation (cats). Propranolol did not show any inhibitory effect on pressor response to norepinephrine and on the contractile response induced by preganglionic sympathetic nerve stimulation. 4. Smooth muscle: Carvedilol produced inhibitory effects on spontaneous motility, and contractile responses to acetylcholine, histamine, nicotine, serotonin and BaCl2 in isolated ileum (guinea pigs). It also inhibited contractile responses to acetylcholine and histamine in isolated trachea (guinea pigs), and spontaneous motility in isolated uterus (rats). Carvedilol reduced norepinephrine-induced contraction of isolated vas deferens at lower concentration (guinea pigs). 5. Digestive system: Decrease in intestinal motility was observed after intravenous administration of carvedilol and propranolol (rabbits). However, carvedilol failed to influence on gastric motility and tonus, whereas propranolol increased them (rabbits). Carvedilol, like propranolol, induced little or no effects on gastro-intestinal transit (mice) and gastric emptying rate (rats). Both drugs decreased gastric secretion at similar dose (rats). Carvedilol at higher doses produced lesion of gastric mucosa, whereas propranolol did not show these effects (rats). 6. Skeletal muscle: In in vitro experiment, carvedilol, like propranolol, reduced the contractile response of diaphragm to nerve and muscle stimulation (rats)...
Hirohashi
M
M
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Takasuna
K
K
Tamura
K
K
Yamaguchi
K
K
Maekawa
K
K
Yamada
S
S
Iwasaki
S
S
Yoshida
M
M
Nomura
M
M
Taguchi
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004569:Electroencephalography; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000927:Anticonvulsants; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol