Key result
Combined administration of cocaine and metanephrine increased cardiovascular responses to isoprenaline, noradrenaline, and sympathetic nerve stimulation in anaesthetized dogs.
Why the study?
Does catecholamine uptake blockade alter cardiovascular responses to catecholamines and sympathetic nerve stimulation in anaesthetized dogs?
Does catecholamine uptake blockade alter cardiovascular responses to catecholamines and sympathetic nerve stimulation in anaesthetized dogs?
Differential catecholamine uptake blockade demonstrates that Uptake1 inhibition enhances noradrenaline responses while Uptake2 inhibition enhances isoprenaline responses in the canine cardiovascular system.
No immediate clinical implications from canine data; leaves open translation of dual uptake blockade effects to humans.
The effects of differential and combined catecholamine uptake antagonism on cardiovascular responses of anaesthetized dogs to isoprenaline, noradrenaline, and electrical stimulation of the left ansa subclavia nerve have been studied. Uptake1 inhibition by cocaine HCl (5 mg kg-1 and 1 mg kg-1 every 45 min) enhanced responses to noradrenaline (0.1 to 2.0 micrograms kg-1 i.v.) and sympathetic nerve stimulation (1 to 20 Hz), but did not affect those to isoprenaline. Uptake2 inhibition by metanephrine (40 micrograms kg-1 min-1) enhanced cardiac responses to isoprenaline (0.05 to 1.0 microgram kg-1 i.v.), but did not significantly alter those to noradrenaline or nerve stimulation. Responses to all agonist interventions were increased by the combined administration of cocaine and metanephrine. Cocaine preferentially enhanced the positive chronotropic cardiac response to noradrenaline, but metanephrine did not differentiate between heart rate and contractility. These results have been discussed in the light of the mechanism of drug action involved.
No takes yet. Share an insight, caveat, or question.
Brown et al. (1979) studied this question. Catecholamine uptake blockade (cocaine HCl and metanephrine) was evaluated on Cardiovascular responses to isoprenaline, noradrenaline, and sympathetic nerve stimulation. Combined administration of cocaine and metanephrine increased cardiovascular responses to isoprenaline, noradrenaline, and sympathetic nerve stimulation in anaesthetized dogs.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: