Imipramine Smoking

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

Substrates Inhibitors Inducers CYP1A2 Acetaminophen, caffeine, clozapine, imipramine, theophylline, propranolol Most fluoroquinolone antibiotics, fluvoxamine, cimetidine Tobacco smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole... 

Drugs that may require dosage reduction with smoking cessation acetaminophen, caffeine, imipramine, oxazepam, penfazocine, propranolol, fheophylline, insulin, prazocin, labetalol... 

The mephenytoin metabolic pathway is utilized by commonly used drugs, such as mephobarbital, hexobarbital, diazepam, imipramine and omepra-zol, but only 3-5% of Caucasians and 8% of Blacks are poor metabolizers of mephenytoin, compared to 15-20% of Chinese and Japanese populations (Kupfer et al., 1988). This enzyme s activity is inhibited by floconazole and fluoxetine and induced by drugs such as barbiturates and nicotine (smoking). 

CYP1A2 caffeine, imipramine, paracetamol, theophylline cigarette smoke, omeprazole cimetidine, ciprofloxacin, enoxacin, fluvoxamine... 

Smoking tobacco reduces the plasma levels of amitriptyline, clomipramine, desipramine, imipramine and nortriptyline, but this does not appear to result in a clinically significant interaction. 

Two studies found no difference between the steady-state nortriptyline plasma levels of tobacco smokers and non-smokers, but others have found that smoking tobacco lowers the plasma levels of amitriptyline, clomipramine, desipramine, imipramine" and nortriptyline. For example a 25% reduction in plasma nortriptyline levels was found in one study, and a 45% reduction in total levels of imipramine and its metabolite, desipramine, was found in another." ... 

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