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Conversely, their blockade leads to uncontrolled release of norepinephrine with an overt enhancement of sympathetic effects at ?1-adrenoceptor-mediated myocardial neuroeffector junctions, resulting in tachycardia and tachyarrhythmia. Selective ?-Sympatholytics ?-Blockers, such as prazosin, or the longer-acting terazosin and doxazosin, lack affinity for prejunctional ?2-adrenoceptors.
A ?-blocker (bradycardia, cardiodepression due to sympathetic blockade) can be effectively combined with nifedipine (reflex tachycardia), but obviously not with verapamil (bradycardia, cardiodepression).

 

The potency of an agonist can be expressed in terms of the concentration (EC50) at which the effect reaches one-half of its respective maximum. Antagonists (A) attenuate the effect of agonists, that is, their action is “anti-agonistic”. Competitive antagonists possess affinity for receptors, but binding to the receptor does not lead to a change in cell function (zero intrinsic activity).
M2 receptors mediate acetylcholine effects on the heart: opening of K+ channels leads to slowing of diastolic depolarization in sinoatrial pacemaker cells and a decrease in heart rate. M3 receptors play a role in the regulation of smooth muscle tone, e.g., in the gut and bronchi, where their activation causes stimulation of phospholipase C, membrane depolarization, and increase in muscle tone.

 

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