MD - MEDICINES BY DESIGN
Alcohols
Reactions for Synthesis
Drugs as Medicines 
The Action of Drugs
Discovering New Medicines
Enzyme Inhibitors as Medicines
Bacteria
The Action of Drugs
In order to understand how drugs, such as alcohol work, it is necessary to something about the human nervous system. The nervous system consists of two parts: the central nervous system (the brain and spinal cord) and the peripheral nervous system (all other nervous tissues which connect with the organs of the body). A simple picture is shown below:
The nervous system consists of thousands of millions of nerve cells called neurons. Neurons consist of a cell body and a long fibre called an axon. These are linked together at connections called synapses. The interconnecting neurons provide an important system of communication in the body. An electrical signal called a nerve impulse travels along the axon until it reaches a nerve ending. There the electrical signal causes release of small messenger molecules, called neurotransmitters, which carry the message across the synapse. Neurotransmitters, released from nerve endings, cross the tiny gap to receptors on the dendrites of another neuron. Neurotransmitters can either excite or inhibit the electrical behaviour of the next nerve.
It is thought that alcohol molecules bind to nerve cells near to receptors. Neurons are more inhibited if ethanol is present and the action of the nervous system is depressed.
Discovering New Medicines
See Also: Introduction to "What's in a Medicine?"
When designing a new medicine, scientists focus on two areas:
- developing a biological understanding of the disease or condition they want to cure
- finding a compound which shows promise, i.e. a 'lead compound'.
Medicines have been developed from natural remedies, e.g. aspirin from willow bark. Some have been discovered by accident, e.g. penicillin. Some have been found from random screening.
Noradrenalione is the neurotransmitter in many of the synapses where nerves join organs in the body. It has the structure:
Release of noradrenaline causes the heart rate to be increased, dilation of the bronchioles and an increase in perspiration. Asthma is a breathing difficulty caused by narrowing or blocking of the bronchioles. Noradrenaline causes the opposite effect, but it cannot be used to treat asthma because it may cause a heart attack. Isoprenaline was designed as it is more selective, but still affects the heart rate. Here is its structure:
In recent years salbutamol has been used which is even more selective and acts only by widening the bronchioles. It has the structure:
The structures of noradrenaline, isoprenaline and salbutamol have a common feature. Their activity depends on the presence of the structural fragment:
This is the group of atoms which is involved in binding to the receptor. It's a case of molecular recognition. The structural fragment fits precisely into the shape of the receptor, and functional groups on both are correctly positioned to interact. The structural fragment shown above is an example of a pharmacophore - a group of atoms which confer pharmacological activity on a molecule. Salbutamol is an agonist - a molecule which behaves like the body's natural substance in the way it binds to a receptor and produces a response. Antagonists are molecules which compete with the natural, active compound for receptor sites but which have no effect when bound.
Enzyme Inhibitors as Medicines
Receptors and enzymes are similar. Both are proteins with precise structures designed to accommodate specific arrangements of atoms on another molecule such as a neurotransmitter or a substrate.
Just as antagonists are used to block receptors, so some medicines work by inhibiting the action of enzymes. An example is captopril which is used to treat high blood pressure.
A protein angiotensin II is a key factor in raising blood pressure. The body creates angiotensin II from angiotensin I using an enzyme. Captopril inhibits the enzyme which catalyses the above reaction.
Bacteria
Some molecules inhibit the action of enzymes present in bacteria. As a result, the bacterial cells do not grow and divide, and infection is prevented. Penicillin is a well-known example. Penicillin set the scene for the development of a vast range of antibiotics. These are compounds, obtained from micro-organisms, which selectively destroy disease-causing bacteria.
Penicillin was originally extracted from mould cultures. Penicillin contains a fused-ring system containing a nitrogen atom and a sulphur atom. The four-membered ring contains a cyclic amide group and is called a Β-lactam ring. The penicillin nucleus has the structure:
Different penicillins have been developed with different properties and ranges of antibacterial activity based on this structure.
Penicillin does not normally attack bacteria that are fully grown or in resting state. It stops the growth of new bacteria by inhibiting the action of an enzyme responsible for constructing the cell wall. Penicillin-resistant bacteria have caused serious outbreaks of infections in hospitals. Chemists have developed new penicillins with modified side chains to counteract this.
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