Tricyclic antidepressants nonselective

The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake (see Figure 12.3). This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, H histaminic and a -adrenergic receptors. Compared with tricyclic antidepressants, the SSRIs cause fewer anticholinergic effects and lower cardiotoxicity. However, the newer serotonin reuptake inhibitors should be used cautiously until their long-term effects have been evaluated. 

Interactions. With nonselective monoamine oxidase inhibitors (MAOI), the monoamine dopamine formed from levodopa is protected from destruction it accumulates and also follows the normal path of conversion to noradrenaline (norepinephrine), by dopamine (J-hydroxylase severe hypertension results. The interaction with the selective MAO-B inhibitor, selegiline, is possibly therapeutic (see below). Tricyclic antidepressants are safe. Levodopa antagonises the effects of antipsychotics (dopamine receptor blockers). Some antihypertensives enhance hypotensive effects of levodopa. Metabolites of dopamine in the urine interfere with some tests for phaeochromocytoma, and in such patients it is best to measure the plasma catecholamines directly. 

NSRI Antidepressants. Nonselective serotonin reuptake inhibitors (NSRI)also block the reuptake of norepinephrine. Several of the old tricyclic antidepressants belong in this category. Imipramine and desipramine reduce REM sleep because of the increased norepinephrine levels at postsynaptic receptors caused by reduced reuptake of norepinephrine. 

To avoid drug toxicity and prevent the precipitation of serotonin syndrome, duration cf effect should be considered when switching between antidepressants (e.g., a MAO inhibitor should not be started for 5 weeks after discontinuing fluoxetine 2-3 weeks should elapse between stopping a nonselective MAO inhibitor and initiating therapy with a tricyclic antidepressant). 

Remember that levodopa is a precursor of norepinephrine and epinephrine as well as dopamine and that norepinephrine and epinephrine are metabolized primarily by monoamine oxidase type A. In the presence of nonselective inhibitors of monoamine oxidases, levodopa may cause a hypertensive crisis. Though not contraindicated in Parkinson s disease, tricyclic antidepressants may interfere with the effectiveness of levodopa. The answer is (D). 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafra-nil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage. 

The tricyclic system is generally attached to a basic terminal amine by a three-atom chain. The chain can be shortened to two atoms with retention of antidepressant activity and a decrease in antipsychotic character. The terminal amine is typically a secondary or tertiary amine, and the amine can be part of an alicyclic ring. In general, tertiary amines are more nonselective with respect to inhibition of... 

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