Possible Interaction: Amitriptyline and Cocaine

“This transport is blocked … psychostimulant drugs cocaine , l- and d-amphetamine, and phenyclidine), neurotoxins (6-hydroxydopamine and N-methyl-…-phenylpyridine (MPP))+), neurotransmitters (epinephrine, norepinephrine, gamma-aminobutyric acid, and serotonin), antidepressants ( amitriptyline , bupropion, desipramine, mazindol, nomifensine, and nortriptyline), and various uptake inhibitors (mazindol, GBR 12783, GBR 12909, and amfonelic acid).”

“ AMI (1.8 micromol/L) modestly inhibited the degradation of COC by 4.2% and of CE by 4.0%.”

“These results suggest that AMI and PA may prolong the half-life of COC and CE in human serum.”

“After cocaine (3 X 10(-5) M) treatment, amitriptyline (3 X 10(-8)-3 X 10(-6) M) antagonized competitively concentration-response curves to norepinephrine, yielding a postsynaptic pKb of 7.51.”

“ Amitriptyline was also observed to increase the release of [3H]norepinephrine from the field-stimulated rat anococcygeus muscle pretreated with cocaine.”

“ Amitriptyline also antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine.”

“However, the increased overflow of [3H]norepinephrine caused by amitriptyline also occurred when neuronal uptake was blocked by cocaine (3 x 10(-5) M) but was abolished when prejunctional alpha receptors were blockade by phentolamine (10(-5) M).”

“4 In the presence of a concentration of cocaine (1.1 × 10−5m) which produced a maximal blockade of the uptake of exogenous noradrenaline the application of amitriptyline still produced an increase in evoked tritium overflow.”