Opioid Med Chem (Adams)

Aromatic Ring

Basic Amine

Tertiary carbon

The general structural features required for mu receptor activity include:

B

Which group is required for receptor binding?

lipophilic

___ opioids penetrates the CNS

True

T/F: Metabolism affects opioid DOA & pharmacokinetics

increases

Bypassing first pass effect __ receptor binding

ester

What function groups on heroin increases lipophilicity?

hydroxyl group a 6-C

Why is codeine a mild analgesic and antitussive agent and not abusive like heroin?

ketone at 6-C

Why are hydromorphone, hydrocodone, oxycodone, and oxymorphone significantly more potent than morphine?

beta-hydroxyl group at 14-C

Why do oxycodone and oxymorphone lack antitussant properties?

allyl or cyclopropylmethyl

What substitution(s) on the amine is associated with antagonist activity?

cyclobutylmethyl

or

cyclopropylmethyl & large substitution at 7-C

What substitution(s) on the amine is associated with mixed agonist-antagonist activity?

no E ring

What structural feature is characteristic of morphinans (e.g. levorphanol, butorphanol, and dextromethorphan)?

(+) 3-methyoxy isomer (mirror image) of levorphanol

Levorphanol and Butorphanol are more potent than morphine (like CRAZY potent). Why is dextromethorphan not more potent and only has antitussive effects?

cyclobutylmethyl substitution on amine

Why is butorphanol a mixed KOR agonist/ MOR antagonist?

levorphanol

Which opioid is a morphinan?

meperidine

Which opioid is a 4-phenylpiperidine?

fentanyl

Which opioid is an anilidopiperidine?

methadone

Which opioid is an open chain diphenyl?

pentazocine

Which opioid is a benzomorphan and is also a mixed kappa agonist/ mu partial agonist?

ester hydrolysis

Why does meperidine have poor bioavailability?

seizures

Meperidine can be metabolized into normeperidine via N-demethylation which causes a risk of ___

nitrogen

Addition of ___ between piperidine ring & phenyl ring increases potency of anilidopiperidines (fentanyl/"fentanils").

methadone

Which opioid has high oral potency, long DOA, and is dosed daily for abstinence syndrome i.e. addiction maintenance?

tramadol

Which drug is a meperidine-like agent?

tramadol

This meperidine-like agent has NE & 5-HT activity

loperamide

This meperidine-like agent has low abuse potential, slow absorption, poor oral bioavailability, too lipophilic to be IV, and treats diarrhea