3.2 Drugs of Abuse Med Chem

Su (he only has three questions on the exam)

leo hollisters criteria for hallucinogens

changes thoughts, mood, and perception

little memory impairment

little stupor (unconsciousness), narcosis (drowsiness), or excessive stimulation

minimal autonomic side effects (dizziness, light leaded, HR issues, GI issues)

non-addicting

classical hallucinogens (meet or do not meet) Hollisters criteria?

meet

classical hallucinogens act on the ____ and produce psychological effects that influence behavior

CNS

classical hallucinogens bind to _____ receptors in the CNS

5HT2

5HT2 receptors regulate

mood, cognition, and perception

what are the two classical hallucinogens structural classes

indole-alkylamine and phenyl-alkylamines

what classical hallucinogen class is this structure?

a. indole -alkylamine

b. phenyl-alkylamine

a

what classical hallucinogen class is this structure?

a. indole -alkylamine

b. phenyl-alkylamine

b

psychomimetic are behaviorally heterogenous, what does that mean?

while they all mimic symptoms of psychosis, they all do so in varying, different, and unpredictable mechanisms

many psychedelics have chemical structures that are very similar to…

neurotransmitters

LSD and LSD like agents share…

common stimulus properties (which means that they produce the same sensations in animals and humans)

almost all Hallucinogens contain a ____ in their structure

N (nitrogen)

what is the purpose of the Nitrogen in hallucinogen structures?

allows for mimicking of 5HT so they can bind to the 5HT2 receptors

all hallucinogens that contain a N are considered to be…

alkaloids

psychedelic compounds have high affinity for _____ receptors

5HT

T/F:

psychedelic compounds only have affinity for 5HT receptors

F (false)

nonclassical hallucinogens are CNS _____

stimulants

nonclassical hallucinogens are _____ stimulants

CNS

PCP is a…

a. classical hallucinogen 

b. nonclassical hallucinogen

b

ketamine is a…

a. classical hallucinogen 

b. nonclassical hallucinogen

b

behavioral stimulants tend to affect…

motor activity, alertness, and energy

amphetamines are…

a. classical hallucinogens

b. nonclassical hallucinogens

c. behavioral stimulants

d. analeptics

e. not hallucinogens

e

cocaine is a/an…

a. classical hallucinogen

b. nonclassical hallucinogen

c. behavioral stimulant

d. analeptic

e. not an hallucinogen

e

why are amphetamines, THC, and cocaine not hallucinogens?

because they only cause hallucinogenic effects after multiple doses

____% of 5HT is distributed in the CNS and the other ___% is distributed in the GIT

a. 20;80

b. 25;75

d. 10;90

d. 50;50

d

T/F:

Genes can play a roll in abusive/addictive tendencies

T (true)

classical hallucinogen general structure

Ar-C-C-N

classical hallucinogen general structure:

Ar meaning

aromatic ring that is a substituted phenyl, 3-indolyl, or substituted 3-indolyl moiety

classical hallucinogen general structure: 

C-C 

ethyl or branched ethyl chain

classical hallucinogen general structure: 

N

primary, secondary, or tertiary amine

N-alkyl tryptamines have ___ onset of action and ____ duration of action

rapid; short

DMT administration methods

inhalation, smoking, injection 

DMT is not active by ____ admin

oral

DMT is a…

indole alkylamine/ N-alkyl tryptamine

what changes to N-alkyl tryptamines confer oral activity?

N-alkyl or N,N-dialkyl substituents are bulky and lipophilic enough

what changes to N-alkyl tryptamines can lead to changes in the potency?

substitution on the benzenoid ring

what two N-alkyltryptamines are found on the skin of frogs

bufotenine and 5-OMe DMT

psilocin is a _____ DMT

4-OH (4 hydroxy)

psilocin has a polar hydroxyl group yet it can cross the BBB, how??

the 4-OH group forms a hydrogen bond with the terminal amine to decrease polarity enough to cross

where can psilocin and psilocybin be found?

mushrooms

what is the phosphate ester of psilocin?

psilocybin

once psilocybin is ingested ,it is rapidly metabolized to…

psilocin

ayahuasca is a _____ hallucinogen

B-carboline and classical

Bcarbolines are indole alkaloids and consist of…

a pyridine ring that is fused to an indole skeleton

examples of B-carbolins

harmine, harmaline, and tetrehydro-harmine

which is more potent, mescaline or LSD?

LSD

LSD induces which three changes in a person?

perceptual, psychic, and somatic

LSD induced perceptual changes

changes in shapes, colors, and heightened sense of hearing

LSD induced psychic changes

changes in mood, depersonalization, visual hallucinations, and altered sense of time

LSD induced somatic changes

nausea, blurred vision and dizziness

phenyl propylamines are made by…

structural modification of mescaline

what structural modification of mescaline leads to the formation of phenyl-propylamines?

adding an alpha-methyl group and deleting or rearranging the position of the methoxy groups

what are the three possible mono-methoxy-phenyl-propyl-amines?

OMA, MMA, and PMA

what does OMA mean?

ortho methoxy analog

what does MMA mean?

meta-methoxy-analog

what does PMA mean?

para methoxy analog

introduction of alpha methyl into mescaline leads to ____ potency

doubled

which of the following is a hallucinogen?
a. OMA of mescaline

b. MMA of mescaline

c. PMA of mescaline

d. none of the above

d

PMA is a _____ CNS stimulant 

weak

di-methoxy-amphetamines (DMAs) are substituted derivatives of…

phenylpropylamine amphetamine

Tri-methoxy-amphetamines (TMAs) are substituted derivatives of…

phenylpropylamine amphetamine

which is more potent, TMA or DMA

TMA

where is the potential metabolic site on DMA and TMAs?

para position

how can you block potential metabolism of TMAs and DMAs?

substituting a methyl group at the para group

substituting the para position with a methyl group on TMA and DMA makes…

DOM

DOM has ____ stability than TMA and DMA

higher

DOM is _____ lasting than TMA and DMAs

longer

DOM is more or less potent than mescaline

more

Amphetamine like action:

main effect

central stimulation, increased energy and attention

Amphetamine like action:

neuromechanism

increases release of DA and NE

Amphetamine like action:

behavioral effects

excitement, enhanced locomotion, addictive potential 

Amphetamine like action:

examples

amphetamine and metamphetamine

DOM like action:

main effects

hallucinations, perceptual distorsions

DOM like action:

neuromechanism

activates 5HT2A receptors

DOM like action:

behavioral effects

hallucinations, sensory distorsions

DOM like action:

examples

mescaline, DOM, LSD

position A is the…

terminal amine

position B is the…

chiral center

position C is…

the alpha-methyl group

fill in the blank #1

N methyl > NH2 > NHR > NR2

fill in the blank #2

S (+) > (+) > R (-)

fill in the blank #3

homologation decreases potency; replacement by H decreases potency

fill in the blank #4

B-OH reduces potency

B=O retains activity and potency

fill in the blank #5

unsubstituted aromatic ring preferred

fill in the blank #6

NH2 > NHR > N2

fill in the blank #7

R(-) > (+) > S (+)

fill in the blank #8

homologation decreases potency, and replacement by H decreases potency

fill in the blank #9

BOH and B=O are not well investigated

fill in the blank #10

2,5 dimethyl-substitution preferred

4-substitutino further modulates activity

classical hallucinogens bind to 5HT receptors and the affinity to these is correlated with…

DOM stimulus generalization potencies and human hallucinogenic potencies

TMA substitution of C-4 with ____ leads to enhanced activity

halogens (F, Cl, Br, I, NO2, SCH3)

TMA substitution of _____ with halogens (F, Cl, Br, I, NO2, SCH3) leads to enhanced activity

C-4

TMA substitution of C-4 with halogens (F, Cl, Br, I, NO2, SCH3) leads to ____ activity

enhanced

TMA activity increases by insertion of ____ at C-4

ME, ethyl, isopropyl

TMA activity is decreased if ____ is inserted on the C-4

bulky or butyl groups

TMAs lose their activity if ____ groups are used at C-4

COOH and OH

c

incorporation of substituents into the aromatic ring of amphetamines leads to…

reduced or loss of psychostimulant activity

4-OH-amphetamine lacks _____ action and is unlikely to ____

central stimulant; cross the BBB

why is 4-OH- amphetamine unlikely to cross the BBB and lack central stimulant action

presence of polar aromatic hydroxyl group