Adrenergic receptors antidepressants

Napamezole (68) is a dihydroimidazole derivative with antidepressant activity probably as a result of its combined a 2 adrenergic receptor blockuig and serotonin uptake blocking proper ties It can be synthesized by Wittig olefination of p-tetralone (65) with diethyl (cyanomethyl) phosphonate (66) and base to give nitnle 67 Imidazoline construction on the latter was smoothly... 

The original monoamine hypothesis of depression states that depressions are associated with a deficiency of catecholamines, particularly norepinephrine, at functionally important adrenergic receptor sites in the brain. Elation conversely may be associated with an excess of such amines. The hypothesis was articulated in 1966 only after the mechanism of action of the tricyclic antidepressant desipramine and of the psychostimulants... 

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Trazodone routinely causes sedation, which is why it is used far more often as an adjunct with other antidepressants for sleep than as a primary agent for the treatment of depression. Priapism is a rare but serious adverse effect in males who take trazodone. In addition, orthostatic hypotension and dizziness are more common with trazodone than with nefazodone because the latter agent has a weaker effect at a-adrenergic receptors and also has a balancing of adrenergic effects owing... 

Their beneficial effects in migraine prophylaxis are independent of antidepressant activity and may be related to downregulation of central 5HT2 and adrenergic receptors. 

Other available antidepressants have unique mechanisms of action that may have an impact on norepinephrine, serotonin, or dopamine indirectly through other mechanisms. For example, mirtazapine s direct antagonism of presynaptic a2-adrenergic receptors results in an indirect increase in central noradrenergic and serotonergic activity. 

Nalepa I, Vetulani J Enhancement of the responsiveness of cortical adrenergic receptors by chronic administration of the 5-hydroxytryptamine uptake inhibitor citalopram. J Neurochem 60 2029-2035, 1993 Nalepa I, Vetulani J The responsiveness of cerebral cortical adrenergic receptors after chronic administration of atypical antidepressant mianserin. J Psychiatry Neurosci 19 (2) 120, 1994... 

A potent antidepressant drug, it does not cause sedation. In CNS it inhibits the neuronal uptake of 5-HT. It shows negligible binding to histaminergic, muscarinic, oq adrenergic receptors, so it is devoid of anticholinergic and hypotensive side effects. 

Analogous to b-adrenergic receptor downregulation, antidepressants reduce 5-HT receptor number but not their affinity (51). 

Mirtazapine has been on the market in the United States since August 1996, and it is available in several other countries. The putative mechanism of action mediating antidepressant activity is the blockade of several serotonin receptors (i.e., 5-HT 2a and 5-HT2c) and a2-adrenergic receptors (172). The latter effect increases NE... 

Banerjee SP, Kung LS, Riggi SJ, et al. Development of beta-adrenergic receptor subsensitivity by antidepressants. Nature 1977 268 455-456. 

Pandey G, Davis JM. Treatment with antidepressants and down regulation of beta-adrenergic receptors. Drug Dev Res 1983 3 393-406. 

In terms of side effects of the tricyclic antidepressants (Table 6—5), blockade of alpha 1 adrenergic receptors causes orthostatic hypotension and dizziness (Fig. 6—30). Anticholinergic actions at muscarinic cholinergic receptors cause dry mouth, blurred vision, urinary retention, and constipation and memory disturbances (Fig. 

FIGURE 6—32. Side effects of the tricyclic antidepressants—part 3. In this diagram, the icon of the TCA is shown with its alpha adrenergic antagonist (alpha) portion inserted into alpha adrenergic receptors, causing the side effects of dizziness, decreased blood pressure, and drowsiness. 

Beta agonists. Beta adrenergic receptors can be rapidly down regulated by agonists and if this is desired for an antidepressant action, beta agonists may be useful. To date, it has not been possible to identify beta 1 or beta 2 agonists that successfully penetrate the brain and yet are not cardiotoxic. Pursuing safer beta 1 and beta 2... 

The Tricyclic Antidepressant has five actions blocking the reuptake of serotonin, blocking the reuptake of norepinephrine, blockade of alpha 1 adrenergic receptors, blockade of H1 histamine receptors, and blockade of muscarinic cholinergic receptors. 

---