The effects of a peripherally selective alpha 2‐adrenoceptor antagonist, MK‐467, on the metabolic and cardiovascular response to exercise in healthy man.

Abstract

4 The insulin and FFA response to exercise was significantly enhanced by although glucose was unaltered by drug. 5 It is concluded that both pre-and post-junctional peripheral a(2-receptors play an important role in the metabolic response to exercise in man.

Insulin Secretion and Glucose Kinetics During Exercise With and Without Pharmacological α1- and α2-Receptor Blockade

“…Therefore, we are unable to offer an explanation for the divergence in the effect of ␣ 2 -receptor blockade on insulin secretion during exercise. The data on plasma insulin concentrations in the present study are in line with those from another study (19), in which a peripherally selective ␣ 2 -receptor antagonist (MK-467) was infused before and during exercise. However, in that study (19), an exerciseinduced decrease in insulin during placebo treatment could not be demonstrated, probably because of an inadequate exercise protocol.…”

“…The data on plasma insulin concentrations in the present study are in line with those from another study (19), in which a peripherally selective ␣ 2 -receptor antagonist (MK-467) was infused before and during exercise. However, in that study (19), an exerciseinduced decrease in insulin during placebo treatment could not be demonstrated, probably because of an inadequate exercise protocol. Finally, the importance of ␣ 2 -receptors in the exercise-induced inhibition of insulin secretion is supported by the study from Natali et al (20), in which selective ␣ 2 -receptor blockade with deriglidole prevented epinephrine-induced inhibition of insulin secretion.…”

“…Individual workloads were targeted at 60% (␣ 1 -receptor blockade study) and 70% (␣ 2 -receptor blockade study) of the previously measured VO 2max . During each experiment, VO 2 was measured by a cardiopulmonary test system (Medical Graphics, St. Paul, MN) before and three times during the exercise (15)(16)(17)(18)(19)(35)(36)(37)(38)(39), and 55-59 min). The first measurement (15-19 min) was used to adjust the workload, which then was not changed during the last 30 min of exercise.…”

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

“…A series of potent and selective α 2 -antagonists, including the berbane (CH-38083 (101) [180]), benzoquinolizine (WY 26703 (102) and WY 27127 (103) [181,182]), benzo [b]furoquinolizine (MK 467 (104) targeted as an antidiabetic [183], and MK-912 (105) acting at central and peripheral α 2 -ARs [184]), and isoquinonaphthyridine (delequamine or RS 15385-197 (106), endowed with an α 2 /α 1 selectivity ratio > 14,000 in binding experiments [185]) derivatives are structurally related to the family of yohimbanes.…”

Potentiation of the anti‐obesity effect of the selective β3‐adrenoceptor agonist BRL 35135 in obese Zucker rats by exercise

“…In humans a2-antagonism increases lipolysis, presumably through increased synaptic noradrenaline concentration . Peripheral a2-antagonism seems to potentiate the lipolytic and plasma noradrenaline increasing effects of exercise in man (Sciberras et al, 1994), suggesting that the combination of physical training with an M2-antagonist might be advantageous when activation of fat tissue metabolism is required.…”