CNS Depressants & Anti-Seizure Drugs

Question 1

drugs that can be used to slow down or depress the functions of the CNS

Answer 1

CNS depressants

Question 2

often share at least one mode of action
-positive modulation of the action of y-aminobutyric acid (GABA) at GABAa receptor complex

Answer 2

CNS depressants

Question 3

aka anxiolytics
reduce anxiety & exert a calming effect

Answer 3

Sedatives

Question 4

-produce drowsiness & encourage the onset & maintenance of a state of sleep
-involve more pronounced depression of the CNS than sedation

Answer 4

Hypnotics

Question 5

major inhibitory neurotransmitter in the brain

Answer 5

GABA

Question 6

deficiency in GABA activity in the CNS is important in the pathophysiology of

Answer 6

anxiety & insomnia

Question 7

2 types of receptors that GABA activates

Answer 7

1- inotropic: GABA a & c
2- metabotropic: GABA b

Question 8

-target for many anxiolytics & sedative-hypnotic agents
-ligand-gated chloride channel
upon activation, Cl- influx is increased & the membrane becomes hyperpolarized, resulting in neuronal inhibition

Answer 8

GABAa receptor

Question 9

GABAa receptor Agonist
increase frequency of opening of the chloride channel

Answer 9

Benzodiazepines

Question 10

GABAa receptor Inverse Agonist
-diminish the positive effect of GABA on chloride flux
-increase anxiety, produce panic attacks, & improve memory

Answer 10

B-carbolines

Question 11

-GABAa receptor Antagonist
-used clinically to counteract the sedative effect of benzodiazepine

Answer 11

FLumazenil

Question 12

benzoDiAzEpines

Answer 12

Di=2
Az=Nitrogen
Ep= 7 membered ring

Question 13

benzodiazepines

Answer 13

-diazepam
-chlordiazepoxide
-flurazepam
-desmethyldiazepam
-oxazepam
-lorazepam
-nitrazepam
-triazolam
-alprazolam

Question 14

Aromatic or heteroaromatic ring A on benzodiazepine is

Answer 14

-required for activity
-aromatic ring > heteroaromatic ring

Question 15

An electronegative substituent at position 7 of Benzodiazepine is required for activity

Answer 15

more electronegative = higher activity
Positions 6, 8, and 9 should NOT be substituted.

Question 16

SAR of Benzodiazepines
A phenyl ring C at position 5 promotes activity
If ortho (2) or diortho (2,6) substituted with EWG =

Answer 16

increases activity

Question 17

SAR of Benzodiazepines
A phenyl ring C at position 5 promotes activity
para substitution =

Answer 17

decreases activity

Question 18

SAR of Benzodiazepines
substitution with a 3-OH group

Answer 18

with 3-OH group: ↓ DOA (short-acting)
without 3-OH group: ↑ DOA (long-acting)

Question 19

SAR of Benzodiazepines
2-carbonyl (C=O) group =
Nitrogen atom at position 1 (N₁) =

Answer 19

important for activity

Question 20

SAR of Benzodiazepines
1,2-fused triazole or imidazole ring =

Answer 20

increased activity tolerance
Short acting

Question 21

Short acting benzodiazepines

Answer 21

Triazolam
Midazolam

Question 22

Intermediate acting Benzodiazepines

Answer 22

Lorazepam
Temazepam
Oxazepam

Question 23

long acting benzodiazepines

Answer 23

Clorazepate
chlordiazepoxide
Clonazepam
Diazepam
Flurazepam
Quazepam

Question 24

Nonbenzodiazepine BzRAs

Answer 24

Zolpidem
Eszopiclone
Zapelon

Question 25

NONBENZODIAZEPINE BzRAs Zolpidem

Answer 25

Imidazopyridine

Question 26

NONBENZODIAZEPINE BzRAs Eszopiclone

Answer 26

-a cyclopyrrolone -S-isomer: primary active hypnotic

Question 27

NONBENZODIAZEPINE BzRAs Zapelon

Answer 27

a pyrazolopyrimidine

Question 28

-play a role in the circadian rhythm -biosynthesized & released by night -promoted commercially as sleep aid -poor hypnotic drug

Answer 28

melatonin

Question 29

-precursor of melatonin -an indole

Answer 29

serotonin

Question 30

an endogenous sleeping neurohormone

Answer 30

melatonin

Question 31

-activate melatonin receptors -more efficacious than melatonin but less efficacious than benzodiazepines as a hypnotic

Answer 31

ramelteon

Question 32

are 5,5-distributed barbituric acids

Answer 32

barbiturates

Question 33

barbituric acid that lacks CNS depressant activity

Answer 33

2,4,6-trioxohexahydropyrimidine

Question 34

replacement of both hydrogens at _________ with alkyl or aryl groups confers activity

Answer 34

position 5

Question 35

SAR of Barbiturates in general, increasing lipophilicity=

Answer 35

-increases hypnotic potency -faster onset of action -shorter duration of action

Question 36

increase in log P=

Answer 36

increase in lipophilicity

Question 37

SAR of Barbiturates increasing the number of carbon atoms at the R5 position=

Answer 37

increases lipophilicity

Question 38

SAR of Barbiturates unsaturation of the alkyl substituents=

Answer 38

increase the lipid solubility secobarbital > pentobarbital

Question 39

SAR of Barbiturates addition of alkyl group at R1=

Answer 39

increases lipophilicity

Question 40

SAR of Barbiturates replacement of oxygen with sulfur at pos 2=

Answer 40

thiobarbiturates *ultra-short acting barbiturates *used as anesthetics, not as sedative-hypnotics

Question 41

thiopental thiamylal

Answer 41

thiobarbiturates *ultra-short acting *anesthetics

Question 42

pentobarbital secobarbital

Answer 42

*short acting *sedatives

Question 43

Amobarbital Butabarbital

Answer 43

intermediate acting *hypnotics

Question 44

mephobarbital phenobarbital

Answer 44

long acting *anti-convulsant

Question 45

miscellaneous sedative-hypnotics

Answer 45

*amides & imides *alcohols & their Carbamate derivatives *aldehydes & their derivatives

Question 46

structurally similar to the barbiturates, especially phenobarbital

Answer 46

glutethemide

Question 47

CNS depressant potency increases up to how many carbon atoms?

Answer 47

maximum 8 carbons decreasing potency if more than 8 carbons

Question 48

ALCOHOLS AND THEIR CARBAMATE DERIVATIVES Branching of the alkyl chain

Answer 48

increases depressant activity tertiary > secondary > primary

Question 49

ALCOHOLS AND THEIR CARBAMATE DERIVATIVES Replacement of a hydrogen atom in the alkyl group by a halogen =

Answer 49

increases activity

Question 50

Carbamylation of alcohols generally

Answer 50

increases depressant potency

Question 51

thought to act principally through a metabolite

Answer 51

trichloroethanol

Question 52

combination of ethanol and chloral hydrate

Answer 52

mickey finn

Question 53

cyclic trimer of acetaldehyde

Answer 53

paraldehyde

Question 54

*are symptoms of disturbed electrical activity in the brain characterized by episodes of abnormal, excessive, and synchronous discharge of a group of neurons within the brain that cause involuntary movement, sensation, or thought *may result from primary or acquired neurological disturbances of brain function as a result of an imbalance between excitatory and inhibitory processes in the brain

Answer 54

seizures

Question 55

derivative of phenobarbital

Answer 55

primidone

Question 56

5,5-diphenylhydantoin

Answer 56

phenytoin

Question 57

prodrug of phenytoin

Answer 57

fosphenytoin

Question 58

oxazolidinediones

Answer 58

trimethadione dimethadione

Question 59

succinimides

Answer 59

ethosuximide methsuximide

Question 60

iminostilbene dibenzazepine derivatives

Answer 60

dibenz= 2 benzenes az= 1 nitrogen ep= 7 membered ring carbamazepine oxcarbazepine

Question 61

benzodiazepines

Answer 61

2 nitrogens in a 7 membered ring diazepam clonazepam

Question 62

gaba analogues

Answer 62

from the gaba structure vigabatrin gabapentin pregabalin

Question 63

valproic acid

Answer 63

broad spectrum anticonvulsant valproic acid valeric acid 5 carbons

Question 64

bis-carbamate

Answer 64

felbamate 2 carbamates linked to 1 benzene ring

Question 65

phenyltriazine

Answer 65

lamotrigine tri az in= 3 N in 6 membered ring

Question 66

sulfonamide type anti anticonvulsant

Answer 66

zonisamide

Question 67

levetiracetam

Answer 67

pyrrolidone derivative an analog of the nootropic agent- piracetam

Question 68

tiagabine

Answer 68

nipecotic acid active moiety