Biomaterial Database

An in vitro quantitative analysis of the alpha adrenoceptor partial agonist activity of dobutamine and its relevance to inotropic selectivity. 1981

T P Kenakin

In rat anococcygeus muscle, dobutamine produced concentration-related submaximal contractions which were antagonized competitively by phentolamine (pKB = 8.3) and dobutamine antagonized norepinephrine-induced contractions in a competitive manner with an equilibrium dissociation constant for the alpha adrenoceptor of 20 nM (pKB = 7.7). Therefore, dobutamine satisfied criteria for a partial agonist of alpha adrenoceptors having an affinity for alpha adrenoceptors 25 times that of norepinephrine (pKA = 6.3) in this tissue. An estimate of the relative efficacy of dobutamine showed one-fortieth the the efficacy of norepinephrine at the alpha adrenoceptors. Dobutamine contracted rabbit aorta and produced concentration-related relaxations at 1000 times greater concentrations after alkylation of alpha adrenoceptors by phenoxybenzamine. In noncontracted canine saphenous vein, dobutamine had no visible agonist activity but did produce contractions after propranolol. In partially contracted saphenous vein, dobutamine produced a small contraction which was converted to a propranolol-sensitive relaxation of tone after phentolamine. Dobutamine was a full beta adrenoceptor agonist in guinea-pig trachea under spontaneous tone but a partial agonist after strong contraction by bethanechol. This allowed measurement of the pKB of dobutamine at beta adrenoceptors (pKB = 5.35) and estimation of efficacy at beta adrenoceptors relative to isoproterenol (eDob/eIso = 1/20). No evidence for beta adrenoceptor selectivity was found in studies of potency ratios and relative efficacy using isoproterenol for comparison. Dobutamine showed a slight (2-fold) selectivity for inotropy in vitro when compared to isoproterenol in guinea-pig right and left atria. This selectivity was removed by phentolamine suggesting a cardiac alpha-like adrenoceptor effect; this finding was confirmed in propranolol-treated guinea-pig left atria. These results are discussed in terms of the in vivo effects of dobutamine and its use as a tool for classification of beta adrenoceptors, particularly the putative presynaptic beta adrenoceptor.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010643	Phenoxybenzamine	An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator.	Dibenylene,Dibenyline,Dibenziran,Dibenzylin,Dibenzyline,Dibenzyran,Phenoxybenzamine Hydrochloride,Hydrochloride, Phenoxybenzamine
D010646	Phentolamine	A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.	Fentolamin,Phentolamine Mesilate,Phentolamine Mesylate,Phentolamine Methanesulfonate,Phentolamine Mono-hydrochloride,Regitine,Regityn,Rogitine,Z-Max,Mesilate, Phentolamine,Mesylate, Phentolamine,Methanesulfonate, Phentolamine,Mono-hydrochloride, Phentolamine,Phentolamine Mono hydrochloride
D011433	Propranolol	A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.	Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002395	Catecholamines	A general class of ortho-dihydroxyphenylalkylamines derived from TYROSINE.	Catecholamine,Sympathin,Sympathins
D004280	Dobutamine	A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.	Dobucor,Dobuject,Dobutamin Fresenius,Dobutamin Hexal,Dobutamin Solvay,Dobutamin-ratiopharm,Dobutamina Inibsa,Dobutamina Rovi,Dobutamine (+)-Isomer,Dobutamine Hydrobromide,Dobutamine Hydrochloride,Dobutamine Lactobionate,Dobutamine Phosphate (1:1) Salt, (-)-Isomer,Dobutamine Tartrate,Dobutamine Tartrate (1:1), (R-(R,R))-Isomer,Dobutamine Tartrate (1:1), (S-(R,R))-Isomer,Dobutamine, (-)-Isomer,Dobutamine, Phosphate (1:1) Salt (+)-Isomer,Dobutrex,Lilly 81929,Oxiken,Posiject,Dobutamin ratiopharm,Hydrobromide, Dobutamine,Hydrochloride, Dobutamine,Lactobionate, Dobutamine,Tartrate, Dobutamine
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog