neurotransmitter = a substance released from one neurone and acting rapidly, briefly and at short range on a receptor in the membrane of another neurone. It may cause excitation or inhibition of the postsynaptic neurone.
neuromodulator (= neuroregulator) there is no good definition, but they usually act slowly, often at a different site from where they were released. They usually increase or reduce neuronal excitability without causing cells to fire; they may also regulate gene transcription. Most neuromodulators are peptides. As they are well conserved in slimy things they are regarded as being phylogenetically old (but the function of many of them appears to have changed in mammals).
The CNS is the most complex organ system in the body: the physiology of the normal CNS is not well understood, and most drugs given for their CNS effects are used empirically. Many more drugs have side effects either directly on the CNS or mediated by it. The action of most drugs at the receptor level is known, but this is not always useful in predicting their effects on the whole animal. These notes concentrate on the major transmitter systems where the information is least confusing.
The effects produced by a neurotransmitter can be very variable for a
number of reasons:
•the CNS is not hard wired - connections are continually changing
under the influence of growth factors. There are usually several back-up
wiring systems - the importance of these can change with time and disease.
Receptors are being continuously recycled - thus their numbers change.
•most neurotransmitters have multiple receptor subtypes at which
they can work - so the effects depend on the receptors present on the
target cell.
•the same receptor subtypes sometimes have different signal transduction
mechanisms coupled to different effectors.
•their effects can be changed by neuromodulators.
The good news is that all neurones are thought to obey Dale’s law
and release the same transmitter at all their terminals (but don’t
forget co-transmittors). Calcium is required for neurotransmitter release,
so drugs which interfere with calcium movement can alter neurotransmitter
function.
Every neurone has a wide range of inputs (usually both excitatory and
inhibitory); what it does will depend on the sum of all these inputs.
Disinhibition
Time course
Excitatory amino acids
Inhibitory amino acids
Monoamines
Other fast transmitters
Neuromodulators
