Possible Interaction: Amphetamine and Prazosin

“Experiment 1 examined the systemic antagonism of methylphenidate-induced impulsivity with either propranolol, a β-adrenoreceptor blocker, or prazosin , an α1-adrenoreceptor antagonist, which antagonises the locomotor activating effects of amphetamine.”

“Phentolamine and prazosin inhibited the direct response to adrenaline, dopamine and amphetamine , and the amphetamine-facilitated response to adrenaline and dopamine; they were inactive against serotonin alone and combined with a facilitating dose of amphetamine or dopamine.”

“Such activity seemed related to a catecholaminergic substrate since the increase of responding induced by amphetamine was blocked by pimozide, d,l-propranolol and prazosin.”

“Preliminary experiments indicated that intraperitoneal injection of prazosin (0.06 mg/kg) reduces the locomotor hyperactivity induced by the peripheral administration of D‐amphetamine (0.75 mg/kg).”

“ Amphetamine (100 nM-10 microM) caused a depolarization that was antagonized by prazosin (100 nM).”

“In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 microM, had an EC50 of 26 microM and a maximum effect of 10 +/- 0.9 mV (N = 8).”

“Subsequent studies showed that the beneficial effects of classical treatments of human narcolepsy amphetamines and tricyclic antidepressants) are antagonized by prazosin , suggesting that these drugs are active through an indirect alpha-1 stimulation (via an increase of norepinephrine in the synaptic cleft).”

“In addition, prazosin , at a dose that did not affect either saline-associated locomotor behavior in mice or the locomotor-activity increase produced by the dopamine uptake inhibitor, bupropion, also antagonized the locomotor stimulation produced by amphetamine and cocaine.”

“The cues produced by amphetamine were antagonized by the selective alpha 1-adrenoceptor antagonist, prazosin , and slightly potentiated by the selective alpha 2-adrenoceptor antagonist, yohimbine.”