Attentional deficitHyperactivity Syndrome

Frequency/prevalence

4 – 6 % of school children

more boys than girls

About 75 % are affected in adulthood

Symptoms

Attention deficit: distractable, problems to concentrate, to finish a taskHyperactivity: inability to remain seated talking too muchImpuslivity: interrupts other spakers can‘t wait for anything antisocial behaviour

No insight into their own disease-state

Cause

There is a strong genetic component

Speculative:Polymorphism of the D4 gene ???of the DA-transporter Gene ???

Environmental factors alone can not explainthe disease

Psychostimulants in ADHD

Amphetamines: Amphetamine (Adderall®)) Methamphetamine (Adderall ®) Methylphenidate (Ritalin ®)

Non Amphetamines: Pemoline (Cylert ®) Atomoxetine (Strattera®) Modafinil

Under Ivestigation:ABT-418 (N-ACH-R-Ago)S-Citalopram (Escitalopram®, Lexapro®)Histamine H3 receptor antagonists (Komater et al. 2002)

1-Methylphenidate: Ritalin ®, Medikinet®, Equasym®, Concerta ® Methadate ®

2-D-AmphetamineDexamphetamine Tx for those who do not respond to Ritalin

3-Adderall ®is an amphetamine coctail

Amphetamines:

Behavioural pharmacology of amphetamine

Self-administered

Dopamine-dependent, mediated by the brain reward system

Dose dependent increase in:-All behaviours resulting in fragmentation of behaviour swichtching – finally stereotypy

Dopamin-dependent, mediated by striatum and N.accumbens

Methylphenidate

• is a derivative of piperidine and is structurally related to dextroamphetamine, an older drug still used to treat AD/HD

Atomoxetine (Strattera®)

• Approved in USA and UK for ADHD in children,

• adolescents and adults.• In Germany: March 2005

• No psychostimulant drug• Contraindication: MAO inhibitors

• Metabolism:• P450 pathway

Atomoxetine: Mechanism of action

• Selective noradrenaline reuptake inhibitor SNARI

• Some selectivity for the prefrontal cortex

• Reboxetine

Atomoxetine effects in humans

1-Mood brightening, but no psychostimulant-like high.

2-Neuropharmacology a-Enhancement of noradrenaline tone b-Facilitates neuronal differentiation during developent c-Facilitates neuronal plasticity d-protects against various neurotoxins.

3-Behavioural pharmacology Alerting effects

Histamine H3-antagonists in ADHD

The H3 receptor is a presynaptic auto- and Heteroreceptor.

It inhibits histamine an Catecholamine release

H3-antagonists enhance catecholamine release

Nicotine-R agonists in ADHD

Nicotinic ACH-Receptors are located

Presynaptically as heteroreceptors on

Catecholaminergic terminals

Nicotine-R-agonists enhance catecholamine

release

ADHD in adulthood

Untreated ADHD persists in about 66% toAdulthood and results in:

adverse/inappropriate/antisocial behaviour

addiction.

Misuse of ADHD drugs as enhancers

For combating sleep

For enhacement of motivation for work

For mood brightening

For cognition enhancement (learning, memory, communication)