Neur 342 - Amphetamines

synthetic psychostimulants related to DA

What are amphetamines?

- cathinone

- ephedrine

Name two similar plant compounds to amphetamines?

L-amphetamines

D-amphetamines

What are the types of amphetamines?

D-amphetamine

Which type of amphetamine is more potent?

3:1 mixture of D-amphetamine to L-amphetamine

What is the mixture of adderall?

class II

What schedule class drug are amphetamines?

~12 hours

What is the half life of amphetamines?

use every few hours for days

What is the pattern of drug use for amphetamines?

Absorption and distribution slide: 7

- liver

- brain

Where does metabolism of amphetamines occur?

CYP enzymes

What enzyme in the liver metabolizes amphetamines?

monoamine oxidase(MAOs)

What enzyme in the brain metabolizes amphetamines?

methamphetamines

What amphetamine is not completely broken down?

amphetamine

methamphetamine is metabolized into what active metabolite?

4-hydroxyamphetamine

What is amphetamine's active metabolite?

excretion -- Slide 9

- increase in BP and HR

- fat breakdown

- arousing/appetite effects

What are the effects of NE?

- body temp increases

- appetite effects

What are the effects of serotonin?

- reinforcement

- addiction

- euphoria

- locomotor activation

What are dopamine effects?

intense "rush" sensation

What are the acute behavioral effects that are immediate after smoking or intravenous injection of methamphetamines?

euphoria w/out "rush"

What are the acute behavioral effects that are immediate after oral or intranasal of methamphetamines?

- nervousness, anxiety

- Punding

- insomnia

Name not so good acute behavioral effects>

grinding of teeth, skin picking, and nail biting

What does Punding involve?

- hallucination

- formication syndrome

- paranoia

What are chronic psychological effects of methamphetamines?

- tooth decay

- weight loss

- cardiovascular and pulmonary dysfunction

What are the chronic physical effects of methamphetamines?

ceramide

methamphetamines increase what levels?

speed up cellular metabolism

- result in faster aging and earlier cell death

An increase in ceramide levels is involved with what?

- block monoamine transporters

- reverse the action of VMAT-2

- inhibit MAO(high dose)

How does amphetamines/methamphetamines increase DA and NE levels in the synapse?

damages and depletes Da and 5-HT neurons

What does a chronic meth use do?

reduces DA in striatum and kills DA in substantia nigra

- motor deficits

Which type of DA neurons does methamphetamines destroy and what does this cause?

- slower motor reactions

- memory impairments

loss of dopamine transporters in METH abusers causes what?

- oxidative stress

- excitotoxicity

- neuroinflammation

- mitochondrial dysfunction

Name the possible mechanism for methamphetamine-induced neurotoxicity?

dependence and withdrawal syndrome

What does chronic methamphetamine use lead to?