Tricyclic antidepressants chemical structure

Shortly after iproniazid was shown to have antidepressant properties, imipramine was introduced as the first tricyclic antidepressant. These drugs received the name tricyclic because their structure contains three molecular rings. At first, imipramine was investigated as a possible treatment for the psychotic episodes associated with schizophrenia, a severe mental disorder that causes hallucinations and delusions, because it was chemically similar to another effective anti-schizophrenia drug. Imipramine did not reduce the severity of psychotic episodes, but it did elevate the mood of the patients who took it. In the late 1950s, it was released in the United States under the name Tofranil for the treatment of depression. 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

It is structurally and chemically related to tricyclic antidepressant drug imipramine and pharmacologically it is similar to diphenyl hydantoin sodium. It is effective in grandmal and psychomotor epilepsy and also in the treatment of trigeminal neuralgia (a condition characterized by paroxysms of intense pain of stabbing nature within the area of distribution of trigeminal nerve without sensory loss). 

These drugs are most commonly classified according to their principal pharmacological effect rather than by specific chemical structure (Table 10.4). The exception to this is the tricyclic antidepressants which share a common chemical structure and also common pharmacological effects. The other important type of drug used in the treatment of mood disorders is the mood stabilisers (lithium compounds and some anticonvulsants) which are discussed in the next section of this chapter. Tricyclic antidepressants... 

The tricyclic antidepressants are the most widely used class of drugs used for clinical depression and are usually the first type of medication prescribed. All of the effects are not uniform throughout this structural class and the actual prescription may involve an evaluation of some of the symptoms exhibited by the patient. Because the chemical... 

The first antidepressants to be discovered came from two classes of agents, namely, the tricyclic antidepressants, so named because their chemical structure has three rings, and the MAO inhibitors, so named because they inhibit the enzyme MAO, which destroys monoamine neurotransmitters. When tricyclic antidepressants block the NE transporter, they increase the availability of NE in the synapse, since the vacuum cleaner reuptake pump can no longer sweep NE out of the synapse (Figs. 5—16 and 5—18). When tricyclic antidepressants block the DA pump (Fig. 5—32) or the 5HT pump (Fig. 5—35), they similarly enhance the synaptic availability of DA or 5HT, respectively, and by the same mechanism. When MAO inhibitors block NE, DA, and 5HT breakdown, they boost the levels of these neurotransmitters (Fig. 5-15). 

The tricyclic antidepressants (Table 6—5) were so named because their organic chemical structure contains three rings (Fig. 6—25). The tricyclic antidepressants were synthesized about the same time as other three-ringed molecules that were shown to be effective tranquilizers for schizophrenia (i.e., the early antipsychotic neuroleptic drugs such as chlorpromazine) (Fig. 6—26). The tricyclic antidepressants were a disappointment when tested as antipsychotics. Even though they have a three-ringed structure, they were not effective in the treatment of schizophrenia and were almost... 

FIGURE 6—25. This is the chemical structure of a tricyclic antidepressant (TCA). The three rings show how this group of drugs got its name. 

Clomipramine has also aroused interest because of an action on prolactin release, which occurs with major tranquillizers but not with other tricyclic antidepressants (289). This action of clomipramine is related to its chemical structure and reflects a greater effect on dopamine metabolism and serotonin uptake compared with other antidepressants. 

The antidepressants available in the United States are classified by either their chemical structure (e.g., the tricyclics, TCAs) or their actions on neurotransmitters (e.g., SSRIs and MAOIs) or simply as other (e.g., Wellbutrin). In the future, the classification of the antidepressants may become more confusing as new drugs are developed that are neither TCAs, SSRIs, or MAOIs. 

Antidepressants generally fall into one of three categories (1) tricyclic antidepressants (TCAs), which are so named because of their three-ring chemical structure (2) selective serotonin reuptake inhibitors (SSRIs), which block only the reabsorption of serotonin and not of norepinephrine and (3) monoamine oxidase (MAO) inhibitors, which inhibit the metabolic breakdown of norepinephrine and/or serotonin. 

Two cases of non-thrombocytopenic purpura occurred in patients taking tricyclic antidepressants. Both improved on withdrawal (107). True thrombocytopenia, with platelets counts as low as 120 x 1012/1, occurred in a 79-year-old woman taking doxepin. During later treatment with amitriptyline, thrombocytopenia recurred, but not when she took imipramine (108). Cross-sensitivity must be highly specific to chemical structure, doxepin and amitriptyline being more like each other than imipramine. 

TCAs (tricyclic antidepressants) antidepressant medications that have three rings in its chemical structure. 

Chemical/Pharmaceutical/Other Class Synthetic iminostilbene derivative structurally similar to imipramine, a tricyclic antidepressant. While unrelated structurally, carbamazepine shares a similar therapeutic action with phenytoin Chemical Formula C15H12N2O Chemical Structure ... 

Representative Chemicals Imipramine Amitriptyline Doxepin Desipramine Nortriptyline Chemical/Pharmaceutical/Other Class The tricyclic antidepressants are a group of drugs that have a three-ring molecular core and share a similar pharmacologic effect, inhibiting the reuptake of biogenic amines at central presynap-tic terminals Chemical Structures ... 

The antidepressant drugs are generally classified according to their chemical structure (e.g., tricyclic antidepressants [TCA]) or according to their pharmacological action (e.g., monoamine oxidase inhibitors [MAOI] serotonin reuptake inhibitors [SSRI]). Certain other antidepressants, which do not fall into the above categories, are sometimes referred to as atypical antidepressants (see below). 

Tricyclic antidepressants were named after their characteristic chemical structure, although a number of the newer drugs in this group have a different chemical structure but still share similar pharmacological profiles. Tricyclic antidepressants inhibit the re-uptake of serotonin and noradrenaline into nerve endings. This leads to a build up of neurotransmitter at receptor sites in synapses. They also reduce the number of some receptors, which may contribute to the therapeutic action, but their complete mechanism of action is unknown. Examples of tricyclic antidepressants include imipramine and amitriptyline (for use of amitriptyline in neuropathic pain see Chapter 12). 

Heterocyclics (second- and third-generation antidepressants) Drugs of varied chemical structures several have actions different from those of tricyclic antidepressants or selective serotonin reuptake inhibitors... 

B. In addition, presumably because its chemical structure is similar to that of the tricyclic antidepressant imipramine, acute carbamazepine overdose can cause seizures and cardiac conduction disturbances. 

---