Alkaloids are a large class of nitrogen-containing secondary metabolites found in a wide variety of natural sources. They contain at least one nitrogen atom, usually within a heterocyclic ring. The term \"alkaloid\" (alkali-like) was coined by W. Meissner in 1819, reflecting their basic chemical nature. The position of the nitrogen atom in the carbon ring varies across different alkaloids and plant families.

Chemical Nature and Physical Properties

• Basicity: Most alkaloids are basic (alkaline), though some, like colchicine, are neutral.
• Natural State: They usually occur as salts of organic acids, such as malic or tartaric acid, within the plant.
• Appearance: Generally, they are colorless, crystalline solids.
• Taste: They typically possess a bitter taste.
• Exceptions: A few alkaloids exist as liquids (e.g., Nicotine, Coniine) or are colored (e.g., Berberine is yellow).
• Toxicity: They are highly poisonous but provide therapeutic activities in low doses. Examples of poisonous alkaloids include strychnine and coniine.

Occurrence and Distribution

Alkaloids are predominantly found in higher plants (Angiosperms), occurring in approximately 20% of vascular plant species.

Occurrence in Nature

• Fungi: For example, Ergot (Claviceps purpurea).
• Animals: Found in rare occurrences in the toxic secretions of certain frogs (poison-dart frogs), ants, and toads.
• Lower Plants: Occasionally found in mosses and ferns, though rarely in algae.
• Plant Forms: In plants, alkaloids exist as free bases, N-oxides, or most commonly as salts of organic acids like malic, citric, or tartaric acid.

Distribution within the Plant Kingdom

Distribution is uneven; certain families are \"alkaloid-rich,\" while others, like Rosaceae, are almost devoid of them.

Key Alkaloid-Rich Families:

• Solanaceae: Tobacco, Belladonna.
• Papaveraceae: Opium poppy.
• Rubiaceae: Cinchona.
• Apocynaceae: Vinca.

Distribution in Plant Parts

Alkaloids can accumulate in any part of the plant, often serving as a defense mechanism:

• Bark: Cinchona (Quinine).
• Leaves: Tea (Caffeine), Tobacco (Nicotine).
• Seeds: Nux-vomica (Strychnine), Coffee.
• Roots/Rhizomes: Rauwolfia (Reserpine), Ipecac.
• Fruits/Latex: Opium (Morphine).

Extraction of Alkaloids

Alkaloids are extracted based on their chemical nature: most are insoluble in water but soluble in organic solvents, while their salts are water-soluble.

1. Stas-Otto Method (General Method)

This is the most common approach. The powdered drug is treated with moisture and an alkali (like ammonium hydroxide) to convert alkaloidal salts into free bases. These are then extracted using organic solvents like chloroform or ether. The solvent is later shaken with dilute acid to move the alkaloids into the aqueous layer as salts, leaving impurities behind.

2. Manske\'s Method

This method is used specifically for alkaloids that are stable in acidic conditions. The plant material is extracted directly with water or alcohol acidified with inorganic acids like HCl. This dissolves the alkaloids as acid salts.

3. Extraction of Volatile Alkaloids

Alkaloids like nicotine or coniine are extracted using steam distillation. The plant material is mixed with an alkali and subjected to steam, causing the volatile alkaloids to vaporize. They are later condensed and collected.

4. Continuous Hot Extraction (Soxhlet)

The powdered drug is placed in a Soxhlet apparatus and extracted using a hot organic solvent. This is efficient for complete exhaustion of the drug but must be avoided for thermolabile (heat-sensitive) alkaloids.

5. Modern Techniques

• Supercritical Fluid Extraction (SFE): Uses CO₂ (implied) as a solvent.
• Ultrasound-assisted Extraction: Uses sound waves to disrupt cell walls.

Identification Tests for Alkaloids

Therapeutic Activity and Pharmaceutical Uses

1. Therapeutic Activities

Alkaloids act on various body systems to treat specific conditions

• Analgesics: Used for severe pain management (e.g., Morphine from Opium, Codeine).
• Antimalarials: Essential for treating malaria (e.g., Quinine from Cinchona).
• Anticancer (Antitumor): Used in chemotherapy to stop cell division (e.g., Vincristine and Vinblastine from Vinca).
• Antihypertensives: Used to lower high blood pressure (e.g., Reserpine from Rauwolfia).
• Antispasmodics: Relieve smooth muscle spasms (e.g., Atropine from Belladonna).
• Stimulants: Act on the Central Nervous System (e.g., Caffeine from Tea/Coffee).
• Antitussives: Used to suppress dry cough (e.g., Codeine).
• Anaesthetics: Used to induce loss of sensation (e.g., Morphine, Codeine).

2. Pharmaceutical Uses

Beyond direct treatment, alkaloids serve several roles in drug formulation:

• Starting Materials: Used as precursors for the semi-synthetic production of more potent or less toxic drugs (e.g., Thebaine used to synthesize Naloxone).
• Standardization Markers: Used in quality control to determine the purity and potency of herbal formulations.
• Local Anesthetics: Used to induce numbness during minor procedures (e.g., Cocaine derivatives).