Chapter 19 Amines and Amides

1. Chapter 19 Amines and Amides 19.4 Amines React as Bases 19.5 Heterocyclic Amines and Alkaloids

2. Amines React as Bases • Like ammonia, amines are weak bases in water. NH3 + H2O NH4+ + OH– ammonium hydroxide CH3—NH2 + H2O CH3—NH3+ + OH– methylammonium hydroxide

3. Neutralization forms Amine Salts An amine salt: • Forms when an amine is neutralized by acid. • Is named by replacing the amine part of the name with ammonium followed by the name of the negative ion. CH3—NH2 + HCl CH3—NH3+ Cl– Methylamine methylammonium chloride

4. Properties of Amine Salts Amine salts are: • Solids at room temperature. • Soluble in water and body fluids. • The form used for drugs.

5. Cocaine • Cocaine is sold illegally as an amine salt. • Cocaine is reacted with NaOH to produce the free amine form known as “crack.”

6. Heterocyclic Amines • In a heterocyclic amine, a five- or six-atom ring contains one or more nitrogen atoms.

7. Alkaloids Alkaloids are: • Physiologically active nitrogen-containing compounds. • Produced by plants. • Used as stimulants, anesthetics, and antidepressants. • Often habit forming.

8. Caffeine Caffeine: • Is a stimulant of the central nervous system. • Is found in coffee beans, tea, chocolate, and soft drinks. • Contains an imidazole ring.

9. Nicotine Nicotine: • Increases the adrenaline level in the blood. • Causes addiction to tobacco. • Contains a pyrrolidine ring.

10. Alkaloids Related to Morphine • Alkaloids such as morphine and codeine are produced by the poppy. • For centuries, morphine and codeine have been used as painkillers. • Heroin is a modification of morphine.

11. Pharmacology • An area of research in pharmacology is to design drugs with some of the characteristics of alkaloids. • The structures of cocaine and morphine are modified to produce anesthesia, but without the addictive side effects.

12. Pharmacology • Parts of the morphine structure that produce anesthesia are found in procaine, lidocaine, and demerol.

13. Nervous System Amines • Derived from amino acids • Neurotransmitters • A nerve can be thought of as transmitting a stimulus from one part of the body to another by means of a moving wave of ions. • When the wave reaches the end of a neuron, it causes the release of a transmitter that migrates to a receptor cell, where it triggers the propagation of another wave. • Neuron → Chemical transmitter → Receptor cell, muscle fiber, or another neuron

14. Acetylcholine • Muscles are sensitive to acetylcholine • Acetylcholine is synthesized from amino acids serine and methionine L-Serine → ethanolamine, amino alcohol HO-CH2-CH2-NH3+ + methyl groups from methionine → choline, another amino alcohol HO-CH2-CH2-N+(CH3)3 → O || acetylcholine, CH3-C-O-CH2-CH2-N+(CH3)3 • Once the desired response has been provoked, the acetylcholine must be removed

15. Catecholamines • Derivatives of dopamine (3,4-dihydroxyphenethylamine) • Precursor is amino acid tyrosine • Include norepinephrinene, epinephrine (adrenaline), L-dopa • Produced in the brain and adrenal gland • These hormones permit the body to react to stress by increasing blood flow to muscles, lungs, and brain. • They also stimulate cellular metabolism.

16. Stimulant Drugs: Amphetamines • Synthetic amines related to β-phenylethylamine • Act as stimulants by mimicking natural brain amines. • Amphetamine has been used for weight reduction (no longer recommended; weight loss was only temporary). • Amphetamine induces excitability, restlessness, tremors, insomnia, dilated pupils, increased pulse rate and blood pressure, hallucinations, and psychoses.

17. Serotonine (5-hydroxytryptamine, or 5-HT) • Found in cells of the central nervous system, where it functions as a transmitter in relation to sleep. • Also produced in the intestinal mucosa. • The drug lysergic acid diethylamide (LSD) probably competes with serotonin, since LSD toxicity can be treated by serotonin administration. • Precursor is amino acid L-Tryptophan.

18. Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamineneurotransmitter • Serotonin - Wikipedia, the free encyclopedia • (http://en.wikipedia.org/wiki/Serotonin) • Serotonin is involved in sleep, sensory perception, regulation of body temperature, etc. • Diets high in carbohydrate lead to high levels of serotonin. • Lots of protein lowers the serotonin concentration. • That may seem strange, because protein has lots of tryptophan and carbohydrates have little. • Protein is only 1% tryptophan. • In the presense of all those other amino acids, little tryptophan reaches the brain. • With a carbohydrate meal, the hormone insulin lowers the level of the other amino acids in the blood, allowing relatively high levels of tryptophan to reach the brain.

19. γ-Aminobutyrate (GABA) • Precursor is amino acid L-Glutamate • Present in high concentrations in the brain • Inhibit synaptic transmission

20. Histamine • Precursor is amino acid L-Histidine • Released as a result of allergies • Causes the expansion of capillaries and edema (probably by constricting the smaller veins that lead to them) • The resulting drop in blood pressure may induce shock • Antihistamines are structurally similar to histamine • Antihistamines can prevent the physiological changes produced by histamine release during allergic reactions