9 Mood brain

Psychotropic drugs: chemical substances that change brain function and result in alterations in perception, mood, consciousness or behavior

Psychotherapeutic agents: licensed psychotropic drug exerting therapeutic benefit

Psychomimetics: affects psyche without therapeutic value (drugs of abuse: e.g. MDMA, Mescalin)

• In the 1950s, the prescribed treatment for high blood pressure was a drug called reserpine; a terrible side effect was soon apparent: the admittedly now calm patients had become severely depressed, bordering on suicidal

• 1951 accidental discovery of the mood elevatory effect of iproniazide (tubercolosis)

• 1952 Identification of MOA (Inhibition of Monoaminoxidase (MAO))

  • non-selective (Tranylcypromine)

  • selective MAO-A-Inhibitor (Moclobemide)

  • MAO-Inhibitors reverse depressive effects of reserpin

—> Monoamine hypothesis of depression

monoamine deficiency causes upregulation of postsynaptic monoamine neurotransmitter receptors, and this leads to an increased sensitivity for NA, DA and 5-HT receptors

• antidepressive (mood elevating)

• psychomotoric activation (motivation),

• depression (sedation) anxiolysis

• less sedation

• less anticholinergic effects

• less arrythmias

• lower risk of intoxication

disorders of thinking, perception and affect, the relationship to the environment

• 10 - 30% remission

• 60% recurrences

• 30% stationary treatment

• 10 – 15% commit suicide

• genetic/organic

  • 50% concordance in identical twins • dopamine-hypothesis

  • other neurotransmitters

  • morphologic / functional correlates

• environment

  • „Vulnerability-Stress-Coping-Model“ (how sensitive are you to developing schizophrenia)

assumption: schizophrenia is due to an enhancement of dopaminergic activity (specifically in mesolimbic areas)

• standard AP are D2-blocker (what about reserpine!?)

• binding affinity is proportional to effectiveness

• clozapine antagonises also D4 and 5HT2 receptors

• risperidone antagonises D2 and 5HT2 receptors

PRO (don’t learn words):

• amphetamine effects in humans —> induction of psychotic symptoms

• bromocriptine/apomorphine effects in animal behaviour —> stereotypic behaviour

• correlation between potency of antipsychotics & D2-receptor affinity

CON:

• lack of evidence for elevated dopamine metabolites

• latency of antipsychotics-induced effects

• possible explanation:

  • initially, elevated DA release

  • D2 receptors↓ and DA release↓ during ongoing treatment

• extrapyramidal symptoms

• hyperprolactinemia sedation

• weight gain

• anticholinergic / adrenergic vegetative side effects

• epileptic seizures

galaktorrhoea= milk production without pregnancy

gynecomastia = breast production

chlorpromazine, haloperidol

pharmacologically:

• Dopamine receptor (D2) antagonist

• Serotonin (5HT2A) antagonist

• binding affinity: D2 < 5HT2A

• D2 / 5HT1A partial agonist

clinically

• improved effectivness against negativ symptoms

• reduced occurence of dyskinesia