Histamine As A Target

Histamine 5.1 is a widespread local hormone. It affects the circulatory system producing arteriolar dilation and increases capillary permeability. The local inflammation and swelling around an insect bite are due to the release of histamine. In the lungs it produces bronchial constriction while in the stomach it stimulates gastric acid secretion. There are four families of receptors of which the H1 H2 and H3 are the best known. There is some evidence for the existence of an H4 receptor. Among...

Benzodiazepines As Anxiolytic Agents

The treatment of anxiety and sleep disorders is dominated by the BZDs. These drugs induce sleep (act as hypnotics) in high doses and lead to sedation and reduced anxiety (anxiolytic) at lower doses. They function by an enhancement of the GABA-mediated inhibition of the CNS and act in an allosteric manner on the GABA receptor. The discovery of the BZDs was both fortuitous in the nature and the timing of their discovery. A number of animal screens for tranquilizers involving relaxing muscle in...

Cancer Chemotherapy

The aim of this chapter is to show how cancer chemotherapy exploits the subtle differences between the normal and the cancerous cell. By the end of the chapter you should be aware of the stages in the development of the cell the role of anti-metabolites in blocking nucleic acid biosynthesis the role of alkylating and intercalating agents in interfering with nucleic acid function the role of anti-mitotic agents in interfering with cell division and the role of specific inhibitors of particular...

Adrenergic Receptor Agonists The Development Of Antiasthma Drugs

Bronchial asthma is characterized by breathlessness and bronchial constriction. It may affect as many as 5 of the population. A number of asthma attacks are initiated by the inhalation of an allergen. This induces an inflammatory response in the lungs and a constriction of the bronchial muscle. Treatment involves reducing the response to the allergen, alleviating the inflammatory response and reducing the bronchial constriction using a bronchodilating agent. Agonists of -ad-renergic receptors...

The Nervous System

The nervous system has two major divisions the central nervous system (CNS) comprising the brain and spinal cord, and the peripheral nervous Scheme 1 Schematic diagram of a nerve ending Scheme 1 Schematic diagram of a nerve ending system that lies outside this (see Scheme 2). The peripheral nervous system can be divided into the motor (functional) and sensory nerves. The motor nerves are further sub-divided into the autonomic and somatic nerves. The autonomic nerves regulate the everyday needs...

Drug Receptor Interactions

Although the Hansch reasoning does apply to the interaction of a drug with its receptor, many of the factors that are considered relate to the substance crossing barriers and entering different cellular phases. When we consider a drug interacting with a receptor or an enzyme system, there are a number of physico-chemical features that must be taken into account. A receptor or an enzyme system comprises a highly structured chiral environment dominated not just by the pockets created by the...

The Classification Of Drugs

Drugs may be classified in a number of ways. One way is in terms of the nature of the disease that they are being used to treat. Thus there are compounds that are used to treat infectious diseases. Second, there are compounds that are used to treat cancers and third, non-infectious diseases. The chemistry of infectious diseases is concerned with the development of drugs to injure an invading organism with minimal injury to the host. The targets are often the differences between the viral,...

The History Of Medicinal Chemistry

There is a long history of plants being used to treat various diseases. They figure in the records of early civilisations in Babylon, Egypt, India and China. The therapeutic properties of plants were described by the Ancient Greeks and by the Romans and are recorded in the writings of Hippocrates, Dioscorides, Pliny and Galenus. Some metals and metal salts were also used at this time. In the Middle Ages various 'Materia Medica and pharmacopeas brought together traditional uses of plants. The...

Opioids As Analgesics

Opium, from the poppy Papaver somniferum, is one of the oldest drugs known to man. Its pain relieving and euphoric properties were known to the Ancient Greeks. Morphine 4.87 was first isolated from opium in 1803 and its structure was established in 1925. Its synthesis was reported in 1952 and the X-ray crystal structure was determined in 1968. It co-occurs with codeine 4.88 and thebaine 4.89 together with a family of benzylisoquinoline alkaloids. Despite its serious side effects, morphine is...

The Sulfonamide Antibacterial Agents

Since some dyestuffs selectively stained micro-organisms, Ehrlich proposed that various pathogenic organisms might be controlled by the selective use of dyestuffs. Over the years, this led to many investigations and to some useful anti-bacterial substances including the acriflavine 6.9 anti-bacterial agents introduced in 1917. In 1909, the organoarsenic compound, salvarsan 6.11 was found to be active against trypanosomiasis (sleeping sickness) and syphilis. Salvarsan was derived from an earlier...

Craig Plots And The Topliss Decision Tree

Various schemes have been developed to exploit the Hansch relationships. In the first, known as the Craig plots, p is plotted against s for a series of different substituents see Scheme 7 . This has the effect of highlighting substituents with potentially similar effects on the Hansch equation. The second scheme is known as the Topliss decision tree. It is based on using the change in biological activity arising from inserting one substituent to suggest the next substituent in order to maximize...