Classification of antidepressants
1. Monoamine Oxidase Inhibitors (MAO-A): pyrlinol ( Pyrazidol ).
2. Non-selective monoamine reuptake inhibitors (mainly oppressive neuronal seizure of serotonin and norepinephrine).
2.1. Tricyclic (classical) antidepressants (TCAs). Tertiary amines: amitriptyline, imipramine ( Melipramine ), clomipramine ( Anafranil ), pipethazine ( Azafen ).
3. Means of selective action.
3.1. Inhibitors of neuronal seizure of serotonin: fluoxetine ("Prozac"), paroxetine ( Paxil ), citalopram ( Sedopram ).
3.2. Inhibitors of neuronal seizure of norepinephrine: maprotiline ( Ludomyl ), atomoxetine ( Strattera ).
3.3. Inhibitors of reuptake of serotonin and norepinephrine: venlafaxine (Venlaxor), duloxetine ( Intreev ), milnacipran ( Ixel ).
3.4. Selective inhibitors of norepinephrine and dopamine reuptake: bupropion ( Wellbutrin ).
4. Serotonin receptor agonists: mianserip ( Lerivon ), trazodone ( Trittico ).
5. Other antidepressants are mirtazapine ( Mirtazonale ), agomelatin ( Valdoxan ).
The mechanism of action of antidepressants is shown in Fig. 4.21.
Tricyclic antidepressants, as a rule, inhibit the reverse neuronal capture of different neurotransmitter amines (norepinephrine, dopamine, serotonin). They are the drugs of choice for the treatment of endogenous depressions. Imipramine is also used to treat urinary incontinence. Imipramine in patients in a state of depression weakens the feeling of fear, apathy, indifference to others, improves mood, increases mental and motor activity, has a "balanced" action.
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Fig. 4.21. The mechanism of action of antidepressants
Amitriptyline shows more pronounced sedative activity. This is the most active antidepressant when agitated depression (depression accompanied by psychomotor agitation).
Antidepressants that selectively inhibit the capture of different monoamines
The tetracyclic antidepressant <>> maprotiline ( Lyudomil ) selectively inhibits the reuptake of noradrenaline into the central nervous system, does not inhibit the reuptake of serotonin. It enhances the pressor action of norepinephrine and epinephrine, has moderate cholinolytic activity. Maprotiline has an anhydrite effect, accompanied by an anxiolytic and mild sedative effect. Apply it in various forms of depression, including reactive, neurotic, cyclothymic, involutional and other conditions accompanied by fear, irritability.(), fluvoxamine, trazodone ( Trittico ) are active inhibitors of reuptake by nerve endings of serotonin, have little effect on the capture of noradrenaline and dopamine . Weakly affect cholinergic and H1-histamine receptors. Serotonin reuptake inhibitors are used in various types of depression (especially with depressions accompanied by fear).
Mianserin ( Lerivon ) does not exert a retarding effect on the neuronal capture of neurotransmitters, as well as on the activity of MAO. Lerivon increases the release of noradrenaline into the synaptic cleft due to the blockade of presynaptic α2-adrenergic receptors; also blocks 5-HT 2 (5-hydroxytryptamine) serotonin receptors of the second type. Holinolytic properties do not. Timanaleptic action is combined with anxiolytic and moderate sedation. Antidepressants of bicyclic structure and other chemical structure were also obtained.
The common property of all antidepressants is their timoleptic effect, i.e. positive influence on mood and general mental state. Different antidepressants differ, however, on the sum of pharmacological properties. MAO inhibitors have a stimulating effect. According to reports, MAO inhibitors are often more effective than other antidepressants (tricyclics), at atypical depression. In imipramine, thymoleptic action is also combined with a stimulating effect, while in amitriptyline, pipethazine ("Azafen") a sedative component is expressed. Pipofezin is the original domestic antidepressant of the tricyclic structure. On pharmacological properties, it is close to imipramine, but does not have anticholinergic activity. Pipofezin has found wide application in the treatment of various depressions.
Antidepressants are selective inhibitors of neuronal seizure, blocking predominantly (selectively) reuptake of serotonin. Fluvoxamine, sertaline (Stimulon), fluvoxamen ( Fevarin ), trazodone ( Trittico ) show a balanced effect on CNS without a pronounced sedative or stimulating effect, have less side effects on the cardiovascular system with prolonged use compared with tricyclic antidepressants.
Antidepressants have found application not only in psychiatric practice. They are used for chronic pain syndromes, for the treatment of a number of neurovegetative and somatic diseases, which can sometimes be considered as a manifestation of "masked" depressions.
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Some tricyclic antidepressants (imizin, amitriptyline) in large doses and with prolonged use may have cardiotoxic effects. A number of tricyclic antidepressants (amitriptyline, fluoracycin, imipramine) has a pronounced cholinolytic activity, which makes it difficult to use them in patients with prostatic hypertrophy, intestinal and bladder atony, glaucoma, and cardiovascular diseases. M-holinoliticheskoe effect of drugs manifested by dry mouth, delayed urination, constipation.
MAO inhibitors often cause CNS excitement, tremor, agitation, insomnia, followed by weakness, lethargy, drowsiness. Orthostatic hypotension is possible, from the digestive tract - nausea, abdominal pain, constipation.
Currently, antidepressants are used to treat almost all mental disorders and diseases, including schizophrenia. The task of a psychiatrist is to select the right preparations. Only half of the patients experience improvement after the first course of therapy, so that the selection of drugs can be called trial and error. New drugs basically differ in contraindications (they are much less) and at a price (it is much higher). The effect of the drug is not immediately apparent - usually between the time of the beginning of the reception and the appearance of a positive effect is not less than 2-3 weeks, although in some cases, positive mood changes may appear in one week. Cancellation of drugs can cause an exacerbation of depression.
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