Tricyclic antidepressants receptor interactions

Psychiatric medicines exert multiple effects for two principal reasons. First, they usually interact with more than one receptor type. There are two ways to look at this. You will often hear a medication with multiple receptor interactions called a dirty drug. This is because the more receptor interactions it has, the more effects, and hence side effects, it produces. As a result, great effort has been made to develop newer medications with fewer receptor interactions and, thus, fewer side effects. This effort has been quite successful with antidepressants, as we have moved from the effective but side effect-laden tricyclic antidepressants to newer antidepressants such as selective serotonin reuptake inhibitors. 

Hj, Hj, and Hj receptors are present in the CNS. Tricyclic antidepressant drugs seem to interact with histamine receptors in the CNS. Histamine receptor subtypes in the CNS and the central neurotransmitter role of histamine have been the subject of many recent investigations. Currently there are three central histamine receptors ... 

Both the older tricyclic antidepressants and the more recent drugs related to fluoxetine owe their efficacy to interaction with receptors for the neurotransmitters epinephrine, serotonin, and dopamine. The... 

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. 

In therapeutic doses, the tricyclic antidepressants also cause a variety of less serious unwanted side effects. Many of these are associated with the ability of many of these drugs to act as antagonists at various monoamine receptors (see Table 8.6 below). Antidepressants interact with a large number of neurotransmitter receptors. Some of the targets listed in Table 8.6 represent multiple subtype for example, 5-HT2 is in fact a composite of effects of 5-HT , 5-Hr , and S-HTgc- (For a... 

This diverse collection has been grouped together mostly because they do not operate as selective serotonin reuptake inhibitors. Instead, each one interacts differently with neurotransmitters that are tied to depression serotonin, norepinephrine, or dopamine. For instance, one of the more popular non-SSRIs, Effexor (venlafaxine), selectively inhibits the uptake of serotonin and norepinephrine, acting on the same molecular machinery as tricyclic antidepressants (TCAs). But, in contrast to TCAs, Effexor shows no affinity for other neurotransmitter receptors and thus has far fewer side effects than the... 

Chronic abuse of alcohol can lead to enhanced activity of cytochrome P450 enzymes and a consequent decrease in tricyclic antidepressant (TCA) serum levels. Central receptor interactions between alcohol and TCAs can cause impaired motor abilities (evident with amitriptyline, clomipramine, doxepin, and nortriptyline). 

B. Interactions Based on Additive Effects Additive interaction describes the algebraic summing of the effects of two drugs. The two drugs may or may not act on the same receptor to produce such effects. The combined use of tricyclic antidepressants with diphenhydramine or promethazine predictably causes excessive atropine-like effects since all of these drugs have significant muscarinic receptor-blocking actions. Tricyclic antidepressants may increase the pressor responses to sympathomimetics by interference with amine transporter systems. 

Various tricyclic antidepressants and SSRIs, including fluoxetine, also bind at 5-HT2A and 5-HT2C receptors (141,142). The role, if any, that is derived from a direct interaction of these agents with 5-HT2 receptors versus their interaction at the 5-HT transporter remains to be elucidated. In general, 5-HT2 antagonists downregulate... 

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