Opioid

• A substance, whether endogenous or synthetic, that binds specifically to opioid receptors and produces morphine like effects

Opiate

• Drugs derived from opium, ie morphine-like non-peptidic structure

Narcotic

• Any drug with potent morphine like effects with the potential for dependence

Structural Model

A Opiates

• Derived directly from opium without modification
• Benzylisoquinalones (lack opioid activity)
• noscapine
• papaverine
• Phenanthrenes
• morphine
• codeine
• thebaine

B Semisynthetic Opioids

• Simple modifications from opiates
• Morphine → heroin (diacetyl morphine)
• Thebaine → naloxone

C Synthetic Opioids

• Based on phenanthrene nucleus but have less rings in structure
• Morphinans (4 rings)
• levorphanol
• Benzomorphines (3 rings)
• pentazocine
• Phenylpiperidines (2 rings)
• pethidine
• fentanyl
• alfentanil
• sufentanil
• remifentanil
• Diphenylhaptenes (2 ring-open chain structures)
• methadone

Activity Model

Full agonist

• Morphine
• Pethidine
• Fentanyl
• Alfentanil

Partial Agonist

• Pentazocine
• Codeine
• Naltrexone
• Methadone
• Dextropopoxyphene

Antagonist

• Naloxone

Agonist-Antagonist

• Pentazocine
• Nalorphine

Common Features

• Generally stereoisomers, only levo form is biologically active
• T shaped
• Polycyclic, all except diphenylhaptenes have a phenylpiperidine nucleus

Alterations to Morphine

• Diacetylation of OH group → ↑ potency by ↑ lipid solubility (heroin)
• Substitution on N17 results in antagonist activity
• Hydroxylation of C14 → complete antagonist
• Phenylethyl substitution on N17 → ↑ potency and lipid solubility

Comparison of Agents

• Click here to download a Word doc with a table comparing opioids
• It includes a blank version
• You should memorise the key points, then fill the details into the blank version once per day until you have it memorised
• It's a grind, but it doesn't take that long to do