CPPS 306 Stimulants

What is caffeine in terms of its structure, what its metabolized by, half life, and how its excreted

Xanthine molecule + 3 methyl groups

Metabolized by liver CYP450

T1/2 = 6 hours

Excreted in urine

How does caffiene work as a stimulant

• A adenosine receptor antagonist (an inhibitory molecule that promotes sleepiness by reducing the amount of Ne, DA, ACh, when binding to its receptor). Caffine blocks adenosine receptors preventing its effect

• Inhibits PDE (which breaks down cAMP, it promotes excitability, NT release) which leads to increased cAMP → wakefulness

How much caffiene does one cup of coffee contain

100-200mg

What are the NATURAL stimulants

Methylxanthines

Ephedrine

What are the SYNTHETIC stimulants

Amphetamine

Atomoxtine

Methylphenidate

Modafinil

Phetermine

What is amphetamine in terms of what its similar to, half life, what it stimulates/blocks, what it acts on

• Structurally related to NE/DA

• T1/2 = 20 hours

• Stimulates the release and blocks the reuptake of NE and DA with less effects on 5-HT

• Inhibits MAO at higher concentrations

• A direct agonist at NE receptors

What is Methylphenidate in terms of ewhat its similar to, half life, how is it a stimulant

Similar to amphetamine

T1/2 = 2 hours

Blocks reuptake of DA and NE

• DA = role in motivaiton, reward, attention, wakefulness

• NE = alertness, vigilance, decrease sleep pressure

  • Together these act as stimulants

What is atomoxetine, in terms of what its used for, half life, effects,

• Approved for treatment of ADHD

• T1/2 = 5-20 hours

• Inhibitis NE transport, and DA transport to lesser extent

  • more stay in the synapse allowing them to exert their effects

• NMDA receptor antagonist

  • excess NMDA activity → distractibility

  • Dampens excessive excitatory noise

What is modafinil in terms of what its used for, half life

• Wakefulness promoting agent + Approved for treatment of narcolepsy

  • T1/2 = 10-12 hours

What is phenetermine; what is it similar to, how its excreted, half life, effects

Synthetic Stimulant

• Similar to amphetamine

• Excreted unchanged by the kidneys

• Half life could be immediate (2h) or sustained release (10h)

• Promote NE and DE release + suppress appetite through satiety center

What is ephedrine; half life, effect

Natural Stimulant

• T1/2 = 3-4 hours

• Indirectly increases activity of NE on adrenergic receptors

What are the adverse effects of stimulants in general

• Abuse potential

• High doses activate the DA “reward" pathway + produce amphetamine psychosis insomnia

• Appetite suppression by noradrenaline

• Suppression of growth hormone release by NE

What percentage of children is affected by ADHD

5-12%

Compare and contrast symptoms of ADHD between males and females

Females = inattentive / distractible

Boys = impulsive / hyperactive

What is the checklist for ADHD diagnosis

Symptoms have to persist for more than 6 months

Onset before age 7

Symptoms present in at least two settings

Avg onset 3 years old

What are some aspects to keep in mind for treatments of ADHD

• Combination of medication and behavioural treatment works best

• Psychostimulants/stimulants are the most commonly used ADHD drugs

What are the lists of drugs for ADHD mentioned in class

Atomoxitine

Amphetamine-dextroamphetamine

Dextroamphetamine

Methylphenidate

How much of the population is affected by narcolepsy

0.3 to 0.5%

What is the cause of narcolepsy

Linked to reduce amounts of protein called hypocretin/orexin which is made in the hypothalamus

What is narcolepsy

Characterized by sleep attacks; enter REM sleep intantly during the day

Hallucinations as falling asleep or waking up

Loss of muscle tone occurs without loss of consciousness in response to strong emotions (cataplexy)

What are the drugs used for Narcolepsy

Armodafinil

Dextroamphetamine

Methylphenidate

Which of the three narcolepsy drugs mentioned is the safest and usually the first to use and why

Armodafinil

• Much less likely to be abused than other stimulants