Pharmaceutical Chemistry: Cocaine and Ester Compounds

Study Notes

Cocaine's chemical name is (1R, 2R, 3S, 5S)-2-Methylcarboxyl-tropane-3-yl-benzoate.
Derived from Erythroxylon coca leaves; semi-synthesized from ecgonine.
Appears as levorotatory, colorless crystals; known for euphoric and stimulant properties.
The tropane moiety is essential for cocaine's activity; removing the benzoyl group results in loss of activity.
Hydrolysis of the carboxymethoxy and benzoate groups leads to ecgonine, causing a loss of cocaine's activity.

Benzocaine's chemical name is ethyl 4-aminobenzoate; has weak anesthetic properties.
Generally non-irritant and non-toxic; primarily used in dusting powders and undergoes hydrolysis to yield p-aminobenzoic acid.

Known as 2-Diethylaminoethyl 4-aminobenzoate; similarly hydrolyzed to p-aminobenzoic acid.
Should not be used with sulfa drugs due to its antagonistic effects.

Includes Tetracaine (2-Diethylaminoethyl 4-butylaminobenzoate), Amylocaine, and Butacone.
Ester-based local anesthetics rely on specific structural properties for effectiveness.

Effective anesthetics usually contain nitrogen in alcohol, acid, or both; aromatic acid is necessary.
Aliphatic alcohols, whether open chain or alicyclic, are commonly used.
Best activity is found with benzoic and p-aminobenzoic acids, while introducing -CH2- groups can decrease efficacy.
The carboxyl group must be conjugated with an aryl group for activity, and the para position is most effective for amino substitution.

Composed of a hydrophilic amino group linked through an amide group to a lipophilic aromatic structure.
Examples include Lignocaine (Lidocaine or Xylocaine), known for stability and prolonged action.
Lignocaine has structural adaptations that improve duration and reduce toxicity; modification can alter efficacy.

Produce controllable, reversible CNS depression resulting in loss of sensation and consciousness.
Stages of general anesthesia include:
- Stage 1: Analgesia (onset of drowsiness to loss of eyelash reflex).
- Stage 2: Excitement (characterized by agitation and irregular vital signs).
- Stage 3: Surgical Anesthesia (ideal for surgery, reflexes do not respond to stimuli).
- Stage 4: Impending Death (apnea to circulatory and respiratory failure).

Divided into inhaled general anesthetics (InhGA) and other categories.
Halothane was popular due to its nonflammable properties but has been largely replaced.
Newer agents have improved stability and reduced risk of complications.

No single pharmacophore; correlation exists between anesthetic potency and solubility in olive oil.
Increased alkane, cycloalkane, or aromatic carbon content enhances potency until a threshold is reached.
Cycloalkanes are generally more potent than straight-chain counterparts with the same carbon count.

Enhances stability and potency while reducing flammability.
Higher atomic mass halogens significantly improve potency.
Fully halogenated alkanes often lose anesthetic activity, except with minimal carbon numbers.

Anesthesia likely results from interaction with multiple receptors influencing cell electrical activity.
Inhaled agents enhance chloride conductance in cells, leading to hyperpolarization and reduced impulse transmission.

Commonly used in dentistry, known as laughing gas; requires high concentrations due to low potency.
Risks of hypoxia arise if used independently without oxygen; synthesized by heating ammonium nitrate.