Psychomotor stimulants: cocaine and amphetamines pt 1

coca plant

cocaine is an alkaloid found in these leaves

native to south america

sigmund freud and cocaine

recommended it for many ailments: treatments of alcoholism, morphine addiction, depression, and digestive disorders and he declared that it was non-addictive if taken orally

coca-cola

coca-cola contained caffeine and cocaine

marketed as an alternative to alcohol during the temperance movement

900,000 in the US meet the criteria for cocaine use disorder

cocaine

converted into HCl salt and is crystalized

water soluble and can be taken orally, intranasally, or by IV

isnt heat stable

smokable cocaine

• mixed dissolved cocaine HCl with baking soda, heat the mixture, then dry it

• free crystals crackle hence the name

• produces profound euphoria

• Far less expensive than cocaine powder

• Antidrug Abuse Act 1986- 1:100 rule crack> cocaine in criminalization and reduced to 1:18 in fair sentencing act

rapid entry to the brain is

important factor in the strong addictiv properities of crack cocaine

cocaine pharm

lipopillic

readily passes through the blood-brain barrier

broken down by enzymes in te blood and liver but not cyp enzymes

rapidly eliminated

short half life (30 mins to 1.5 hrs)

high lasts only for 30 mins

due to rapid elimination

drug tests only look for metabolities for cocaine

metabolities of cocaine

benzoylecgonine

cocaethylene

benzoylecogonine

detected in the urine for several days

cocaethylene

cocaine and alcohol produce a unique metabolite

• has biological activity that is similar to cocaine and has a longer half life

cocaine is a

monoamine inhibiter

• blocks DA, NE, 5HT

cocaine binds with the highest affinity to

5 HT transporter

blocking DA reuptake appears the most important

for cocaine’s stimulating, reinforcing, and addictive properties

how do we know it is inhibition of DA reuptake that mediates the psychoactive effects?

SSRIs and SNRIs do not produce psychostimulant effects

DAT KO mice display no further cocaine induced increase in activity

SERT KO and NET KO show cocaine induced increases in activity

destruction of NET nerve fibers has little effect on psychostimulant effects of cocaine

destruction of DAT nerve fibers does not produce psychostimulant effects of cocaine

mechanisms of actions of cocaine

inhibits voltage-gated Na+ channels, making it act like a local anesthetic

prevents transmission of signals along sensory nerves

Schedule II drug

Procaine and lidocaine are some of its derivatives

potent vasoconstrictor