174 Heterocycles in Medicine
Phenobarbitone (another barbiturate, also known as phenobarbital) and a newer drug lamotrigine are used to treat
epilepsy. Trazodone is a useful antidepressant with fewer side effects than some of the older drugs.
Antipsychotic agents, acting primarily as dopamine and 5-HT antagonists, are used mainly to treat schizophrenia.
Newer agents such as olanzapine (page 167) and risperidone have fewer side effects than the traditional phenothiazines
such as chlorpromazine.
The neurodegenerative states present a challenge for medicinal chemistry. Parkinson’s disease is caused primarily by a
defi ciency of dopamine and so dopamine agonists are effective in alleviating some of the symptoms. Riluzole is the only
drug so far developed to have a signifi cant effect in treatment of motor neurone disease.
Other enzyme inhibitors
COX (cyclooxygenase) enzymes are involved in the fi rst stage of prostoglandin synthesis and their inhibition is the
basis of action of the Non-Steroidal Anti-Infl ammatory Drugs (NSAIDS). There are two types of enzyme, COX-1 and
COX-2 – inhibition of the latter results in anti-infl ammatory and analgesic effects while inhibition of the former is
responsible for side-effects, particularly gastric bleeding. Most older NSAIDS have both COX-1 and COX-2 activity
(indomethacin is an example), but etodolac shows very good selectivity for COX-2. Highly selective COX-2 inhibitors
such as celecoxib are now at the forefront. Ketorolac has a different balance of analgesic and anti-infl ammatory proper-
ties and is particularly useful for topical administration to the eye.