To be recognized as a neurotransmitter, a chemical compound must satisfy six conditions: It must be





synthesized in the neuron, stored there, released in sufficient quantity to bring about some physical effect; when administered experimentally, the compound must demonstrate the same effect that it brings about in living tissue; there must be receptor sites specific to this compound on the postsynaptic membrane, as well as a means for shutting off its effect, either by causing its swift decomposition or by reuptake, absorbing it back into the cell.



A hormone, by definition, is a compound produced by an endocrine gland and released into the bloodstream where it can find it's target cells at some distance from it's actual site of release. A neurotransmitter on the other hand is a compound released from a nerve terminal.



When an electrical impulse travels to the end of a nerve cell, it stimulates the terminal of this cell to secrete a chemical signalling molecule at a special junction between nerve cells called a synapse. These nerve terminals are in direct apposition with their target cells to ensure rapid and specific delivery of the signal. This mode of transmission is in general much faster than the endocrine transmission mentioned above.



Both target cells possess receptors for the signalling molecule and may produce identical biochemical responses, it's just a question of the release mechanism that determines whether or not a given molecule is a neurotransmitter or a hormone. So, in the case of adrenaline, it's a hormone when the adrenal gland releases it into the bloodstream and it goes to the heart or the lungs OR it's a neurotransmitter when it is released from a stimulated presynaptic nerve cell and acts on it's neighbouring postsynaptic cell.

In 1950, a chemist at Rhône-Poulenc, a French pharmaceutical company, modified the structure of an antihistamine and accidentally created a drug that can eliminate the psychotic thinking of people with schizophrenia. Within a few years the drug became world famous as chlorpromazine (Thorazine), the first truly effective medication for a disabling mental disorder. Because of its dramatic effect, chlorpromazine set a new course for psychiatry for the rest of the twentieth century.





The great success of chlorpromazine stimulated vigorous competition from other pharmaceutical companies. In the 1950s, the search for more antipsychotic medications led to the accidental discovery of two other types of phsychiatric drugs. First Geigy, a Swiss pharmaceutical company, came up with a modified version of one of its antihistamines that, although useless against psychosis, proved to be a valuable treatment for severe depression. Named imipramine (Tofranil), it paved the way for many contemporary antidepressants. Then Hoffman-La Roche, another Swiss company, created chlordiazepoxide (Librium), which doesn’t help psychosis either but does relieve anxiety. It was soon followed by another benzodiazepine, diazepam (Valium), which became the best-selling drug in America for about a decade, beginning in the mid-1960s.



Adding to the excitement over these drugs were a flurry of findings about their effects on neurotransmitters, a class of brain chemicals that transmit signals between nerve cells. By the 1970s it was discovered that chlorpromazine blocks certain actions of a neurotransmitter called dopamine; imipramine augments the actions of several neurotransmitters, including norephinephrine and serotonin; and diazepam amplifies the effects of yet another neurotransmitter, called gamma-aminobutyric acid [GABA]. In each case, the net result is a change in signaling in brain circuits that control emotional aspects of behaviour.



These discoveries spurred a search for other chemicals that would have similar effects on neurotransmission but fewer undesirable side effects than the originals. The search paid off in a stream of new medications that patients perfer. The most famous, fluoxetine [Prozac], was initially identified as a chemical that prolongs neurotransmission by serotonin; it was subsequently shown to be an effective treatment for both severe and moderate depression. Called an SSRI (selective serotonin reuptake inhibitor), it prolongs serotonin’s effects by inhibiting its reuptake by the nerves that release it, which is the normal way that serortonin signaling is terminated. Related drugs, including sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa) soon followed.



Neutrotransmitters

Found a number of fascinating stories of how neurotransmitters were discovered and sketches of what these things do.



Acetylcholine: