Neuropharmacology of 5-hydroxytryptamine.
This review outlines the history of our knowledge of the neuropharmacology of 5-hydroxytryptamine (5-HT; serotonin), focusing primarily on the work of U.K. scientists. The existence of a vasoconstrictive substance in the blood has been known for over 135 years. The substance was named serotonin and finally identified as 5-HT in 1949. The presence of 5-HT in the brain was reported by Gaddum in 1954 and it was Gaddum who also demonstrated that the action of 5-HT (in the gut) was antagonised by the potent hallucinogen lysergic acid diethylamide. This provoked the notion that 5-HT played a pivotal role in the control of mood and subsequent investigations have generally confirmed this hypothesis. Over the last 50 years a good understanding has been gained of the mechanisms involved in control of the storage, synthesis and degradation of 5-HT in the brain. Knowledge has also been gained on control of the functional activity of this monoamine, often by the use of behavioural models. A considerable literature also now exists on the mechanisms by which many of the drugs used to treat psychiatric illness alter the functional activity of 5-HT, particularly the drugs used to treat depression. Over the last 20 years the number of identified 5-HT receptor subtypes has increased from 2 to 14, or possibly more. A major challenge now is to utilise this knowledge to develop receptor-specific drugs and use the information gained to better treat central nervous system disorders.
Green
A Richard
AR
Global Discovery CNS and Pain Control, AstraZeneca R and D Charnwood, Bakewell Road, Loughborough LE11 5RH. richard.green@astrazeneca.com
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects / Q000266:history / Q000502:physiology; D012701:Serotonin / Q000266:history* / Q000502:physiology; D018490:Serotonin Agents / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use; D006113:United Kingdom
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin