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Drugs and Receptors
Actions for ‘4. Drugs and Receptors’
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So far we have established that the action potential and epsp’s and ipsp’s are caused by opening channels for ions in the neuron’s membrane. Voltage changes in the membrane open voltage-dependent channels to trigger an action potential, and neurotransmitters from an axon bind to receptor molecules in a dendrite or cell body to open ligand-gated channels to trigger an epsp or ipsp. Ligand is another name for transmitter, and for action potentials and epsp’s the channels are gates for sodium ions.
There’s one more complication: Ionotropic, or ligand-gated, receptors operate more simply than metabotropic, or g-protein-coupled, receptors.
Imagine you are a transmitter molecule that wants to open a door for ions to enter into a house. If your hand fits the doorknob (receptor), the door opens and ions can enter. That’s how an ionotropic receptor works. Metabotropic receptors are a variation on the ligand-gated theme. After the transmitter binds to a receptor, a mechanism is set in motion inside the neuron to open a channel for ions at another place nearby. When the transmitter binds with a metabotropic receptor it’s as if you, the transmitter, had to ring a doorbell rather than grasping a doorknob. That sets in motion a mechanism inside to bring someone to open the door, which is located to one side of the doorbell, so the ions can troop in. Now for drugs.
Drug Actions
Drugs may influence synapses as neurotransmitter agonists or antagonists. Drugs may act as agonists to facilitate the synthesis of transmitter or block its reuptake so that more transmitter is available. Or they may block the synthesis and release of transmitters as antagonists.
Drugs may also act on receptors for transmitters by stimulating (agonist) or blocking (antagonist) them. Drug actions are often specific to the receptors for a particular transmitter.
Drug actions on the brain have effects on behavior. Unfortunately we can’t predict a behavioral effect of, say, a receptor blocker unless we know the brain system on which the drug is acting. When we have some idea of the site of action, we can sometimes make predictions, such as that cocaine, amphetamine, and methylphenidate will have similar effects despite differences in their actions. However, it’s a good idea to keep in mind the principle that all drugs have multiple effects. Although we classify drugs by their main effects—as stimulants, hallucinogens, and so on—we must not forget their “side” effects, which could be lethal.
Dose-Response Curves
So far I hope you will agree that drugs act at synapses to produce most of their effects on behavior. However, a physician will not prescribe a drug on the basis of the amount that will reach synapses in the basal ganglia or hypothalamus. Instead, the dose is based on the concentration of the drug (in milligrams per kilogram of body weight) and the body weight of the patient (in kilograms). How gross.
This means of dosing a patient works because of dose-response curves, which show the average result on a behavioral measure of different doses of each drug. The dose that is effective for half of the subjects is called the median effective dose, or ED50. The lethality of a poison is expressed by its median lethal dose, or LD50.
Please respond to either of the following:
In the comedy Arsenic and Old Lace, two elderly sisters poisoned their gentlemen roomers with elderberry wine that contained arsenic. (The wine also contained strychnine and a pinch of cyanide, but let’s ignore those.) They got no help from their nephew, played by Cary Grant; but then, he knew nothing of median effective doses or dose-response curves. Since you do, what advice could you give the elderly sisters to make sure the wine was lethal without wasting a lot of arsenic?
Videos 5 & 6 do not distinguish between a drug’s actions at a synapse and its effects on behavior. The psychoactive drugs we are concerned with have multiple effects: For example, cocaine and alcohol affect behavior in more than one way. How may a single drug produce multiple effects on behavior and the mind? (For hints, look at just the table (chart) showing how actions are linked to effects. Does a drug always have a single action, or a transmitter a single effect? Look at the Army’s concern about this when it evaluated some mind-enhancing drugs for soldiers.)
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