2. PSYCHOTROPIC AGENTS,
ACTIVATING PSYCHIC PROCESSES
(PSYCHOANALEPTICS)
ANTIDEPRESSANTS
(THYMOANALEPTICS) – from Greek thymos –
soul, spirit, mood; ana – prefix, meaning
movement up; lepticos – able to perceive,
delicate, fine
PSYCHOSTIMULANTS (PSYCHOMOTOR
STIMULATORS)
NOOTROPIC AGENTS
(NEUROMATABOLIC STIMULANTS)
3. ANTIDEPRESSANTS
(from Greek anti
- against; Latin depressio - inhibition
Are preparations, the main effect of which is
elimination of depressive syndrome,
improvement of mood, return of interest in
life. (The drugs do not increase mood in
healthy persons).
Depression (from Latin Depressio- pressing, inhibition) is inhibited
psychic state. Symptoms are amotivational melancholy, dramatic
alarm, sensation of despair, blame, tension, alarm, disorder of sleep,
appetite, different somatic complaints
4. Development of depression is related with
serotonin and noradrenalin deficiency.
Serotonin is called neuromediator of “good
mood”, as it regulates impulsive desire, sex
biahavior, change of sleep cycles, facilitation
of falling asleep, decreases aggressiveness,
perception of pain.
Noradrenalin participates in maintenance of
wakefulness, cognitive and adaptive
reactions
5. MECHANISM OF ACTION
MECHANISM OF ANTIDEPRESSANT ACTION IS
RELATED WITH INFLUENCE ON METABOLISM OF
MONOAMINES IN THE CNS
They increase amount of monoamines, disturbing
their neuronal recapture (reuptake) into presynaptic
endings or their inactivation under the influence of
MAO.
6. MECHANISM OF
ANTIDEPRESSANT ACTION
is determined by their influence on
storage, metabolism
and neuronal recapture of monoamines
(noradrenalin, serotonin)
CNS (vesicles in
presynaptic
membranes)
Deaminated
monoamines undergo
metabolism under
influence of MAO
7. CLASSIFICATION
(ACCORDING TO CHEMICAL STRUCTURE)
Drugs of tricyclic structure
Imipramine Amitriptyline
Doxepin
Of tetracyclic structure
Pirlindol Metralindol
Maprotiline
Of other chemical structure
Trazodone Nialamide
8. CLASSIFICATION
(ACCORDING TO MECHANISM OF ACTION)
I. Inhibitors of neuronal recapture (reuptake) of
monoamines
A. Preparations of non-selective action (block neuronal
recapture of serotonin, noradrenalin, dopamine)
( of tricyclic structure)
Imipramine Clomipramine
Pipofezine Amitriptyline
Opipramol Fluacizine Nortriptiline
(of heterocyclic structure) AMOXAPINE
B. Inhibitors of neuronal recapture (reuptake) of serotonin
and noradrenalin
Milnacipran
9. C. Preparations of selective action (block neuronal
recapture (reuptake) of mainly one mediator)
Blocking neuronal recapture (reuptake) of serotonin
Trazodone Fluoxetine
Fluvoxamine Sertraline
Paroxetine Citalopram
Blocking neuronal recapture of noradrenalin
Maprotilin Desipramine
Doxepine Reboxetine
10. II. Blockers (inhibitors) of monoamine
oxydase ( МАО )
МАО has a few isoenzymes –
МАО-А и МАО-В
МАО-А deaminates serotonin, noradrenalin,
tyramine; МАО-В deaminates dopamine,
tyramine, triptamine
МАО-А function in neurons, mucous membrane of
the intestine and liver. Isoenzyme of digestive tract
oxidizes phenylalanine, tyrosine and tyramine of
food. Activity of МАО-В is determined only in
astrocytes.
11. A. Non-selective inhibitors (block МАО-А and
МАО-В)
а) of irreversible action /hydrazide derivatives/
Nialamide Fenelsine
б) of reversible action / non-hydrazide
derivatives / Tranilcipramine
B. Selective (reversible) inhibitors (block mainly
МАО-А)
Pirlindol Befol
Moclobemide Metralindol
Tetrindol Feprosidnin
14. Antidepressants with regulating (balanced)
influence on the CNS
The preparations take activating action in
inhibition, and sedative action in anxiety
Trimipramine Pirazidol
Maprotiline Clomipramine
Sertraline Citalopram
Mirtazapine
15. Pharmacological effects:
Antidepressant is the main one
The dugs can produce the following effects:
Sedative
Activating
М-cholinolytic (atropine-like)
Analgesic
Antihistaminic
α -аdrenoblocking
16. PHARMACOKINETICS
In oral intake MAO inhibitors are rapidly absorbed, tricyclic
drugs - some worse. They are distributed over all organism .
About 50% of introduced dose is eliminated during 2 days in
average, mainly by kidney; the rest part is bond with plasma
proteins and eliminated in 2 weeks only.
(Rate of drug elimination from an organism determines
frequency of dose)
They well penetrate trough blood-brain barrier, placenta and
to breast milk
They are metabolized by hydroxylation with liver enzymes
Many matabolites are active and play significant role in
formation of therapeutic effect
TAD have linear dependence between their content in
plasma and clinical effectiveness (but it is not determining
moment in the treatment of patient)
17. Indications
Depressive states of different origin
Panic states
Social phobia
Nervous anorexia and bulimia
Catalepsy, narcolepsy (attacks of sleep)
18. Dose regimen
Most antidepressants are administered 1-2
times per a day (dependently on Т ½ )
Preparations with sedative action are
mainly administered at bed time, and
drugs with stimulant properties – in the
morning and at daytime
Clinical effect depends in 2-3 weeks of
their use in adequate doses.
19. ADVERSE EFFECTS
determined by block of М-
cholinoreceptors (atropine-like): dryness
in mouth, a decrease of sweet secretion,
tachycardia, disorders of eye accommodation,
constipation (atony of the intestine), urinary
retention (atony of urinary bladder)
The symptoms are reversible and disappear in
decrease of drug dose or its discontinuation.
Cardio-vascular system disorders
arrhythmia, slowing down of atrio-ventricular
conduction (up to full АV-block), orthostatic
hypotension (due to block of α1-receptors)
20. Neurological disorders: tremor, dysarthria,
sleepiness or insomnia, convulsions
Psychic disorders: inhibition of thinking, mental
confusion and disorientation in the place, time, an
increase of alarm, enchancement of hallucinatory-
delusional syndrome
Metabolic – endocrinal disorders: an increase of
body weight due to an increase of appetite, (a decrease
of appetite can be too), dysmenorrhea, disorders of sex
function (a decrease of libido)
Withdrawal syndrome
21. ATYPICAL ANTIDEPRESSANTS
take mainly direct influence on receptors. Improvement of mood is
related with potentiation first of all serotonin effects, and noradrenalin
Mianserine (lerivon) Together with
antidepressant effect it has tranquilizing and
sedative action.
It does not produce atropine-like effect, cardiac
arrhythmia, memory disorders. Effects are related
with block of presynaptic α-2 adrenoreceptors.
Tianeptine (coaxil)
influences serotonin metabolism in brain neurons
(hippocamp), increases neuronal recupture. It has
anxiolytic action (eliminates fear, alarm)
22. DRUG INTERACTION
Antidepressants can change action of other
preparations
E.g.: TAD increase action of opioid analgesics,
antiarrhythmic agents, pressor effects of direct
adrenomimetics
MAO inhibitors are incompatible with some food,
containing tyramine
So-called tyramine, or «cheese» reactions
(hypertonic crisis, cardiac arrhythmia, disorders of
cerebral blood flow
23. POISONING
Clinic of overdosage (poisoning)
coma, metabolic acidosis, inhibition of breathing,
convulsions, cardiac arrhythmia or block can be
observed.
The treatment: β-adrenoblockers, lidocaine (in
cardiac arrhythmia)
sodium hydrocarbonate, КCl (in metabolic acidosis)– to
increase binding of antidepressants with proteins and
prevent their penetrability into tissues)
physostigmine (in atropine-like effect),
diazepam (elimination of convulsions)
24. PSYCHOSTIMULANTS
(psychotonic preparations)
are preparations, stimulating all main functions of
brain, activating physical and psychic (mental)
working capacity.
They eliminate sleepiness, tiredness, elevate
mood, stimulate muscle activity, mobilize energetic
and functional resources in apathy, inertia,
decrease tiredness in healthy people. (Drugs, used
to embolden healthy persons, are called dopes –
English to dope – to give narcotics)
They are called
Psychomotor stimulants
25. Psychostimulants have the following
features:
Rapid effect development (in a few
minutes)
Short-term action
The drugs of consumptive action regarding
brain cells (they exhaust energy resources
of brain)
26. CLASSIFICATION
(according to chemical structure)
Purine (methylxanthine) derivatives
CAFFEINE and drugs containing it
Phenylalkylamine (amphetamine) derivatives
AMPHETAMINE (phenamine)
METHYLPHENIDATE HYDROCHLORIDE
(centedrin)
Sydnonimin
MESOCARB (sydnocarb)
Adamantane derivatives
BROMANTAN
27. MECHANISM OF ACTION
Mechanism of action is different in different
drugs.
Phenylalkylamines:
stimulate release of catecholamines (mainly of
noradrenaline and dopamine) into synaptic cleft
from presynaptic endings and also block their
neuronal recapture
Purines: block adenosine (purine) A1-receptors
of brain
28. Pharmacological characteristics of
preparations
Caffeine group
Caffeine is alkaloid, containing in tea leaves,
coffee-beans, cacao.
It produces the following central effects:
Psychostimulant effect (direct stimulant
action on brain cortex)
Analeptic (life-enhancing) action – it
stimulates respiratory and vasomotor
center of medulla oblongata
29. Caffeine stimulates n.vagus center
Caffeine has both central and peripheral action.
Central and peripheral effects of caffeine can be
opposite
Action on the heart – * stimulant – direct
(peripheral)
* inhibitory – central
(action on n.vagus center)
Action on vessels –* dilation of vessels -
direct (peripheral) action
* narrowing of vessels -
central action (activation of
vasomotor center)
30. Final Caffeine effect on vessels is determined by
their initial state and depends on their localization
Vessels of the heart and kidney is mainly dilated,
brain vessels are more frequently narrowdd
Cafeine takes bronchodilatory action (relative is
aminophylline)
Caffeine increases diuresis
Caffeine stimulates pepsinogen and hydrochloric
acid secretion
Caffeine increases fatty lipids and glycerin content
31. Caffeine stimulates glycogenolysis and lipolysis
Caffeine causes tolerance, dependence
USE: for overcoming of tiredness, sleepiness and
temporary increase of physical and mental
working capacity. It is used as analeptic – for
stimulation of breething and cardio-vascular
functioning.
Adverse effects: nausea, vomiting, anxiety,
increased excitability, insomnia.
In large doses caffeine can cause opposite effects
(sleepiness, «beyond» inhibition of the CNS)
32. Phenylalkylamines
The most strong psychostimulants
Markedly influence catecholamine metabolism
Peripheral (adrenomimetic) effects are very
evident
AMPHETAMINE can be accumulated, cause drug
dependence and tolerance
- Increase excitability
- Inhibit sense of hunger
- Stimulates psychic and physical working
capacity
Use: the treatment of narcolepsy, encephalitis
consequences, asthenic syndrome
33. Sydnonimins
SYDNONIMIN (sydnocarb) has mild
psychostimulant effect
- The effects develops gradually and lasts for a
long period of time
- They do not take marked psychomotor
excitement
- It has property of adaptogen
34. NORMOTHYMIC AGENTS
(THYMOISOLEPTICS)
- drugs, able to decrease circulatory disorders of
affective sphere (fluctuation of mood), and at
prophylactic use prevent development of depressive
and maniacal symptomatology.
Preparations of normothymic action are:
• Lithium salts (carbonate, gluconate, chloride, citrate,
oxybate, prolonged lithium preparations);
• carbamazepine derivatives (carbamazepine);
• valproic acid
• blockers of calcium channels (verapamil, nifedipine)
36. The main pharmacological properties of
nootropic drugs are:
1. Improvement of memory
2. Improvement of learning capability
3. Stimulation of thinking
4. Antihypoxic action
5. Anticonvulsive action
6. They improve transmission of information
between cerebral hemispheres
7. They improve energetic processes in the brain
and its blood supply
37. The main indications for their
administration are:
Memory disorder
2. Decrease of attention
3. Emotional lability
4. Dementia due to impair of cerebral blood flow,
traumatic brain injury, Alzheimer's disease,
dementia in elderly patients
5. Coma due to stroke, trauma, intoxications
6. To treat patients with chronic alcoholism
7. Cerebral atherosclerosis
38. The main mechanisms of nootropic drug action.
Increase of GABAergic system activity of brain.
GABA is the main inhibitory neuromediator in brain
and it influences on metabolism in brain too. It also
can stimulate enzymes of Krebs cycle.
Normalization of the level and balance of
neuromediators in the brain
Increase of protein, ribonucleic acid and ATP
synthesis in the brain
Improvement of glucose metabolism in the brain
Antihypoxic action due to increase of blood flow
and oxygen content in the brain
Stabilization of cell membranes
39. Pharmacodynamics and pharmakokinetics of
Piracetam
Piracetam is a nootropic drug which positively
influence on metabolism and cerebral blood
flow. It increases glucose metabolism, improves
microcirculation in ischemic zones of brain,
inhibits platelet aggregation.
Piracetam improves memory, thinking and
learning capability in case of their disorders. It
takes antihypoxic and moderate anticonvulsive
effects.
40. It has a good absorbability from the small
intestine and penetrability through tissue
barriers such as blood-brain barrier and
placental barrier.
Piracetam is accumulated in frontal lobes,
parietal lobes, occipital lobes and in cerebellum
mainly. Its half-life is 4 - 5 hours. It is excreted
with urine in the active form.
