Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium.

Article Details

Citation

Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S

Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium.

Br J Pharmacol. 1999 Jun;127(4):895-902.

PubMed ID
10433496 [ View in PubMed
]
Abstract

1. Negative inotropic effects of several beta-adrenoceptor (betaAR) antagonists on electrically-stimulated right atria, left atria, right ventricles and left ventricular papillary muscles from reserpine-treated rats were used as a measure of their inverse agonist activities. 2. Beta1AR antagonists acebutolol, atenolol and metoprolol, beta2AR antagonist ICI-181,551 and nonselective betaAR antagonists alprenolol, nadolol, propranolol and timolol produced negative inotropic effects, which were most marked on the right atria. 3. The nonselective betaAR antagonist pindolol did not exhibit inverse agonist activity but inhibited the negative inotropic activities of ICI-118,551, atenolol and propranolol. 4. The negative inotropic effects of lidocaine, nifedipine and pentobarbitone were similar on all the four myocardial preparations. 5. The positive inotropic efficacy of salbutamol on right and left atria but not on right ventricles and papillary muscles was comparable to that of isoprenaline. The antagonist activity of ICI-118,551 against isoprenaline was greater on right atria than on other cardiac regions. 6. Beta1AR proteins were expressed in all regions of the heart but of beta2AR were primarily localized in the right atrium. 7. It is concluded that beta2AR play a greater role in right atria than in other cardiac regions and almost all betaAR antagonists behave as inverse agonists.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AcebutololBeta-2 adrenergic receptorProteinHumans
Unknown
Partial agonist
Details
AlprenololBeta-1 adrenergic receptorProteinHumans
Yes
Antagonist
Details
NadololBeta-1 adrenergic receptorProteinHumans
Yes
Antagonist
Details
NadololBeta-2 adrenergic receptorProteinHumans
Unknown
Antagonist
Details
PindololBeta adrenergic receptor (Protein Group)Protein groupHumans
Unknown
Inhibitor
Details
TimololBeta-1 adrenergic receptorProteinHumans
Yes
Antagonist
Details