Synaptic actions of serotonin

Mirtazapine has a novel mechanism of action that in theory should promote anxiolytic effects, although evidence from studies of anxiety disorders is awaited. It increases synaptic release of serotonin and noradrenaline via blockade of presynaptic inhibitory a2-adrenoceptors, as well as blocking post-synaptic 5-HT2 and 5-HT3 serotonin receptors and Hi histamine receptors. Mirtazapine has good efficacy for anxiety symptoms associated with depression (Fawcett and Barkin 1998), and in controlled studies was superior to... 

Stanford IM, Lacey MG. Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors, on GABA-mediated synaptic input to rat substantia nigra pars reticulata neurons in vitro. J Neurosci 1996 16 7566-7573. 

When fluoxetine or other effective but less specific serotonin uptake inhibitors are given, a rapid decrease in serotonin turnover occurs and the rate of firing of single neural units in the serotonin rich raphe area of the brain is reduced. This decrease in serotonin turnover and release may be a compensatory mechanism in response to an enhanced action of serotonin on the synaptic receptors. 

Reserpine inhibits the synaptic vesicular storage of the monoamines dopamine, serotonin and noradrenaline. As a result they leak out into the cytoplasm where they are inactivated by monoamine oxidase this causes their long-lasting depletion. The resulting low levels of dopamine underlie the antipsychotic actions of reserpine (Chapter 11), whereas the reduced noradrenaline levels underlie its antihypertensive actions. Finally, the resulting low levels of serotonin and noradrenaline mean that reserpine also induces depression. These severe side effects mean that reserpine is no longer used clinically as a treatment for schizophrenia (Chapter 11). 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

Mechanism of Action A tricyclic antidepressant, antianxiety agent, antineuralgic agent, antipruritic, and antiulcer agent that increases synaptic concentrations of norepinephrine and serotonin. TIicrapcuticEffect Produces antidepressant and anxiolytic effects. 

Mechanism of Action A tricyclic antidepressant that increases synaptic concentration of norepinephrine and/or serotonin by inhibiting their reuptake by presynaptic membranes. Therapeutic Effect Produces antidepressant effect. 

As outlined previously, initial biological hypotheses of mood disorders were derived from the pharmacological actions of antidepressant drugs, which increase synaptic concentrations of noradrenaline (NA] and/or serotonin. Consequently, the biogenic amine hypothesis was formulated, but it lacks consistent proof that NA and/or serotonin release is indeed diminished. This failure is in part a result of the limited access to relevant brain areas. Measurements of NA and serotonin and their metabolites in blood, urine, and CSF... 

Depending on the drug and its form, CNS stimulants are usually taken either orally as a solid or tea or by the chewing of leaves, by injection, by smoking, or by snorting. Injection directly into the bloodstream or inhalation of smoke into the lungs induces a very rapid onset of action. CNS stimulants induce their effects by increasing the synaptic concentrations of several neurotransmitters, particularly norepinephrine (noradrenaline), dopamine, and serotonin. They stimulate the release of neurotransmitters and block their reuptake. 

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