Tricylic antidepressants

Since the introduction of tricylic antidepressants (TCAs) almost 50 years ago, monoamine reuptake inhibitors with greatly improved safety profiles have significantly enhanced the treatment of depression [2,3]. Although TCAs are very effective antidepressants, cardiovascular, anticholinergic and sedative side effects... 

Selective serotonin re-uptake inhibitors such as paroxetine tend to cause less antimuscarinic side-effects and are less toxic in overdose than the tricylic antidepressants, such as amitriptyline. However, selective serotonin re-uptake inhibitors are more likely to cause gastrointestinal disturbances, such as nausea and vomiting, than tricylic antidepressants. Selective serotonin re-uptake inhibitors and tricylic antidepressants are equally effective. 

Selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants are equally effective. Hov/ever, SSRIs tend to have fewer antimuscarinic side-effects and are less cardiotoxic in case of overdosage. SSRIs tend to cause gastrointestinal side-effects. Both SSRIs and tricylic antidepressants exhibit a time lag before the action of the antidepressants becomes effective. 

Amitriptyline is a tricylic antidepressant and these have antimuscarinic side-effects, such as urinary retention, blurred vision, dry mouth and sweating. They also tend to cause drowsiness. 

Tricylic antidepressants such as amitriptyline cause antimuscarinic side-effects, such as dry mouth and constipation. These antidepressants also tend to exhibit... 

The synthesis of 614, a conformationally rigid analogue of the tricylic antidepressant imipramine, also begins with an A,A-diisopropyl nicotinamide ortho metalation (Scheme 181) [87H(26)3165]. Thus, LiTMP depro-... 

P155) (114) arrhythmias. Induced by drugs including antiarrhythmics (quinidine), antipsychotics (chlorpromazine), psychotropics (tricylic antidepressants), macrolide antibiotics (clathromycin), HI antihistamines (terfenadine, astemizole) (113) deletions mutations create defective ion channel receptors (115)... 

Among the tricylic antidepressants, imipramine, 54, was the first commercially available drug, which was introduced in 1960 [9],... 

In ALS, emotional lability or pseudobulbar affect can limit social interactions and quality of life. While there are no currently FDA approved therapies for pseudobulbar affect in ALS, SSRIs, tricylic antidepressants and dopaminergic therapy can be beneficial (Gordon and Mitsumoto, 2006). One randomized controlled trial showed that a combination of dextromethorphan and quinidine reduced emotional lability and improved quality of life in ALS (Brooks et al., 2004). 

F ig U re 11.12 Multidimensional chromatogram of tricylic antidepressants in blood plasma. Extraction column and extraction, recovery and wash eluents as in Fig. 11.11. Analytical column Spheri-5, RP-18,22 cm x 4.6 mm i.d. Analytical eluent 0.08 M SDS-56% (v/v) acetonitrile-32% methanol-0.08% triethylamine in 0.09 M phosphate buffer at pH 3.0. Compounds doxepin (DOX), desipramine (DES), nortriptyline (NOR), imipramine (IMI) and amitriptyline (AMI). Reprinted from Ref 48 with permission of Elsevier. 

Antidepressants can be crudely divided into three classes the monoamine oxidase inhibitors (MAOIs), the tricylic antidepressants (TCAs) and related compounds, and the selective serotonin reuptake inhibitors (SSRIs). HPLC-ED did not feature in a review of methods for five leading SSRIs citalopram, fluoxetine, fluvoxa-mine, paroxetine and sertraline. More recently, Clement et measured venlafaxine (Figure 6.17) and 0-desmethylvenlafaxine by HPLC with coulometric... 

In order for medications to be effective, they must be taken at an adequate dose (see figure 14-D). There seems to be a threshold effect, with subtherapeutic doses producing little or no benefit. However, achieving effective doses may be difficult due to the side effects of tricyclic antidepressants and MAOIs. Blood levels may be helpful to check the adequacy of tricylic dosage (see figure 14-E). 

The concept of selective blockade of monoamine reuptake has been studied extensively by Carlsson and associates who have shown that tricylic amines such as imipramine and chlorimipramine are selective inhibitors of 5-HT uptake. Furthermore, they have suggested that blockade of 5-HT reuptake is associated with the "mood-elevating" action of the tricyclic antidepressants and that blockade of NE reuptake promotes "drive" in depressed patients. This is consistent with the fact that chlorimipramine, the most potent and selective inhibitor of 5-HT reuptake in this series, has encouraging antidepressant activity in humans with at least one report of a selective mood-elevating effect.78... 

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