Possible Interaction: Cocaine and Norepinephrine

“Background—Although the sympathomimetic actions and cardiovascular complications of cocaine are ascribed to inhibition of norepinephrine (NE) reuptake, this hypothesis has not been tested in humans.”

“Conclusions—In healthy cocaine-naive individuals, cocaine can inhibit NE reuptake in the human peripheral circulation.”

“We asked (a) whether cocaine can inhibit NE reuptake in the human peripheral circulation and (b) whether the NE-mediated peripheral vasoconstriction is the main mechanism mediating blood pressure-raising effect of cocaine.”

“Plasma epinephrine and norepinephrine concentrations were significantly increased in response to cocaine injection compared to placebo.”

“ Cocaine is a potent vasoconstrictive agent that blocks re-uptake of norepinephrine at the adrenergic nerve terminals.”

“There is a concentration gradient for NA decreasing from the corneal periphery towards the centre, but not for DA or AD.Reduction in NA loading after incubation with cocaine demonstrates the presence of functional sympathetic nerves.”

“Acute intra-peritoneal injections of cocaine (20 mg/kg body weight) to rats resulted in increased NE uptake by prefrontal cortex (PFC) synaptosomes with a parallel increase in the surface expression of endogenous NET.”

“ Cocaine binds NET and modulates NE transport.”

“ Cocaine acts by inhibiting dopamine, noradrenaline and serotonin [5-hydroxytryptamine(5-HT)] reuptake.”

“Recent evidence suggests that NE systems may interact with DA systems to augment the activational effects of psychostimulant drugs, such as cocaine or amphetamine, and DA/NE interactions may play a key role in the capacity of psychostimulants to suppress eating.”

“In rabbit iris dilator, desensitization occurred to repeated oxymetazoline application at … the agonist activity was complete in about 3 h. Exposure to cocaine (10 μmol/l), hydrocortisone (100 μmol/l) and … pmol/l), significantly potentiated the response to norepinephrine by 92-, 32- and 7 …, pigmented rabbit and human, respectively.”

“However, chronic use of cocaine or ephedrine may deplete norepinephrine from sympathetic nerve terminals, leading to priapism.”

“ Cocaine also binds to the dopamine transporter (DAT) and to the noradrenaline transporter (NET) and inhibits presynaptic reuptake of dopamine and noradrenaline.”