opium

Raw Opium

The air-dried latex obtained by incision from the unripe capsule of Papaver somniferum (Papaveraceae).

Number of alkaloids in opium

40 alkaloids.

Minimum morphine percentage in opium

Not less than 10%.

Minimum codeine percentage in opium

Not less than 2%.

Acid opium alkaloids form salts with

Meconic acid.

Significance of Meconic acid detection

Its detection, even in small amounts, indicates the presence of opium.

Meconic acid chemical name

β-hydroxy, α-α-dicarboxy-γ-pyrone.

Test for Opium (Meconic acid test) steps

FECl3 red color which does not disappear on addition of 0.25 ml of dil HCl.

Phenanthrene alkaloids examples

Morphine, Codeine, Thebaine.

Benzylisoquinoline alkaloids examples

Papaverine, Noscapine.

Phenethylamine alkaloids examples

Narceine.

Morphine (optical activity and chemical group)

Phenolic and laevorotatory.

Morphine solubility in water, chloroform, ether, benzene

Insoluble.

Morphine solubility in alcohol

Slightly soluble.

Reason morphine is soluble in fixed alkalies

Because it is phenolic.

How to precipitate morphine from acid solutions

By addition of ammonium chloride, ammonium sulphate, or NH4OH at pH 9.

Main clinical uses of morphine

IV opiate agonist, narcotic analgesic.

Apomorphine formation

When morphine is heated at 140°C under pressure with HCl.

Apomorphine depressant action on CNS

Little depressant action.

Other actions of apomorphine

Emetic and expectorant.

Apomorphine use in Parkinson's disease

Subcutaneously, due to its dopamine-like action.

Heroin (chemical name and formation)

Diacetylmorphine, formed by acetylation of morphine.

Dionine chemical name

Ethylmorphine.

Dionine uses

Analgesic effect, ophthalmic eye drops, and helps avoid withdrawal symptoms.

Fentanyl (type of opioid and potency)

Synthetic opioid, 50-100 times more potent than morphine.

Common side effect of morphine, apomorphine, heroin, dionine, fentanyl

Breathing problems.

Nitrous acid test for morphine identity

If morphine salt solution in hydrochloric acid is treated with sodium nitrite crystals and the solution rendered alkaline with potassium hydroxide, a rose red colour is produced.

Another application of Nitrous acid test for morphine

Colourimetric determination of morphine.

Ferric chloride test with morphine color

Greenish-blue color.

Significance of Ferric chloride test for morphine vs. codeine

Distinguishes morphine from codeine (codeine gives no color).

Codeine chemical composition

Methyl ether of morphine.

Codeine solubility compared to morphine

Comparatively more soluble in water, ether, benzene, chloroform, and ethanol.

Is codeine phenolic?

No, it is non-phenolic.

Does codeine form phenates with alkalies?

No.

Codeine with ferric chloride color

No color.

Reason codeine base remains dissolved in aqueous phase after alkalinization

Because the alkaloid base is water soluble.

Primary use of Codeine syrup

For dry, unproductive cough.

Mechanism of action for codeine's antitussive effect

Activation of the μ-opioid receptor in the CNS.

Papaverine optical activity

Optically inactive.

Papaverine oxalate use in alkaloid separation

Insoluble in water, used for separation from other opium alkaloids.

Therapeutically used salt of papaverine

Papaverine hydrochloride.

Primary pharmacological action of Papaverine

Vasodilator.

Papaverine mechanism as vasodilator and effect on blood pressure

Relaxes smooth muscles in blood vessels, causing dilation, which lowers blood pressure.

General conditions Papaverine treats

Conditions causing spasm of smooth muscle.

Noscapine (Narcotine) optical activity

Laevorotatory (optically active).

Does Noscapine possess narcotic properties?

No.

Another name for Noscapine (due to lack of narcotic properties)

Anarcotine.

Characteristic structural feature of Noscapine

Lactone ring.

Noscapine solubility in cold vs. hot alkali hydroxide solutions

Insoluble in cold alkali hydroxide but dissolves in hot ones due to the opening of its lactone ring.

Pharmacological activities of Noscapine

Antineoplastic activities and anti-tussive effect.

Mechanism of action for Noscapine's anti-tussive effect

Activation of sigma opioid receptors.

Narceine optical activity

Optically inactive.

Functional groups in Narceine

Carboxylic group and a ketonic group.

Reason Narceine is soluble in alkali hydroxides

Because it contains a carboxylic group.

Compounds Narceine forms with alcohol

Esters.

Reactions Narceine undergoes due to ketonic group

Reacts with phenyl hydrazines to give hydrazones, and with hydroxylamines to give oximes.

Narceine identification test (color changes)

1. Crystal of narceine + resorcinol/C.H2SO4 → yellow color. 2. Warming on water bath → crimson red. 3. Cooling → blood red to orange yellow color.

First step in opium alkaloid isolation

Maceration of opium with water for 24 hours (with CaCl2).

Insoluble residue after initial maceration

Calcium meconate.

Alkaloids in filtrate after initial maceration (HCl salts)

Morphine (M), Codeine (C), Papaverine (P), Noscapine (No), Narceine (Na).

Step after obtaining Alkaloidal HCl salts for separation

Add alkali, then filter.

Alkaloids in filtrate after alkali addition and filtration

Morphine (M), Codeine (C), Narceine (Na).

Alkaloids in residue after alkali addition and filtration

Papaverine (P), Noscapine (No).

Separation of Papaverine (P) and Noscapine (No) from residue

Treat with boiling water, then oxalic acid, then filter.

Alkaloid as residue after boiling water/oxalic acid treatment

Papaverine (P).

Alkaloid in filtrate after boiling water/oxalic acid treatment

Noscapine (No).

Separation of Morphine (M), Codeine (C), Narceine (Na) from filtrate

Add CHCl3.

Alkaloids in aqueous layer after CHCl3 addition

Morphine (M) (as phenate salt) and Narceine (Na) (as sodium salt).

Alkaloid in CHCl3 layer after CHCl3 addition

Codeine (C).

Separation of Morphine (M) and Narceine (Na) from aqueous layer

Acidify, then add NH4OH.

Alkaloid as residue after acidifying and adding NH4OH

Morphine (M).

Alkaloid in filtrate after acidifying and adding NH4OH

Narceine (Na).

SAR Feature 1 (nitrogen)

A tertiary nitrogen, with the group on the nitrogen being relatively small.

SAR Feature 2 (central carbon C13)

A central carbon atom (C13), of which none of the valences is connected with hydrogen.

SAR Feature 3 (aromatic group)

A phenyl group or a group isosteric with phenyl which is connected to the central carbon atom.

SAR Feature 4 (carbon chain)

A two-carbon chain separating the central carbon atom from the nitrogen for maximal activity.

Key structural change converting narcotic agonist to antagonist

Alkylation of the piperidine nitrogen (replacement of the methyl group by propyl, allyl, or isopropyl).

Naloxone (Narcan) primary uses

IV opiate antidote, used to reverse overdoses of heroin and other opioids.

Nalorphine primary uses

Used to reverse respiratory depression from narcotic overdoses and in the diagnosis of physical dependence on opioids