Acetylcholine is perhaps the best-understood neurotransmitter in
medicine. Acetylcholine" is made from choline which can be synthesized in the
liver, although choline is often available in the diet and can be supplemented.
The parasympathetic system uses acetylcholine as the neurotransmitter and is
found everywhere in the body. For example, acetylcholine sends signals to muscle
cells to contract. In the brain, acetylcholine has arousal functions in the
right amounts but tends to cause depression in overdose. Alzheimer's disease is
associated with declining levels of acetylcholine and degeneration of neurons
which use this neurotransmitter.
Increasing acetylcholine activity arouses
thinking, memory, and computational abilities, but too much may make us feel
depressed. Several antidepressant drugs block acetylcholine circuits and, if
taken in overdose, produce stupor and coma by acetylcholine blockade.
Physostigmine is a drug which works like acetylcholine and awakens the comatose
patient immediately, although the effect is short-lived and must be repeated.
The administration of choline, the acetylcholine precursor may improve memory
but too much may also produce fatigue or depression. A spontaneous experiment in
neurochemistry occurred when two students reported to an emergency room with
marijuana intoxication and were given physostigmine intravenously. The
attending physicians thought that they would be aroused from their stupor.
Instead, they both experienced a prompt and profound depression with thoughts of
suicide. After the experience, they expressed new empathy for those who feel
suicidally depressed. The combination of marijuana and increased acetylcholine
circuit activity is a formula for instant despair.
Smoking increases nicotine levels in the brain with initial stimulation of acetylcholine
circuits and later blockade. This dual action produces the typical biphasic
response of an addictive drug with initial psychomotor stimulation followed by inhibition. The drive to smoke is
essentially a drive to maintain brain nicotine levels. Nicotine is
accompanied by a complex of toxic chemicals including carbon monoxide, benzene,
and polycyclic hydrocarbons which can depress brain function. Smokers cannot
expect to have clarity of consciousness, nor stable moods.
symptoms are generated by acetylcholine mechanisms, especially nausea, vomiting,
belching, cramps, defecation, sweating, and runny nose. Nicotine mimics
some the actions of acetylcholine and even veteran smokers who chew nicotine
gums for the first time may get these effects
Drugs which block acetylcholine
activity are popular in medicine and have many uses. .Atropine is the prototype
and along with related compounds has been used in medicines to treat upset GIT
function. Atropinic drugs reduce secretions and block crampy abdominal pain from
vigorous contractions of intestinal smooth muscle. Too much atropine and you are
dry-mouthed, constipated, and have trouble urinating; you may also have trouble
thinking and remembering. In the lateral hypothalamus, acetylcholine is the
transmitter of predatory aggression and prey-killing. Atropine tends to block
this form of aggressive behavior. It is interesting to note that some
antidepressant drugs have strong atropinic activity. Predatory aggression
is different from territorial aggression which is organized by noradrenalin
circuits (fight and flight). Drugs which block this activity (beta-blockers)
have found many medical applications including lowering blood pressure,
preventing migraine, calming racing hearts, and reducing anxiety and aggression.
(Induction of severe depression by physostigmine in
Marajuana intoxicated individuals. Br. J. Addiction 1973; 68: 321-325}