There are many ways in which drugs can interfere with impulse transmission. Suppose that the chemical structure of a drug is very similar to the structure of a neurotransmitter in the body. If the degree of similarity is great, then the drug molecules will bind to the receptors and “deceive” the neuron, causing it to react in the same way as a real mediator. This is how many drugs work (this is called mimicry). For example, morphine and heroin exert their effects due to their similarity with the recently discovered endorphin.
The narcotic effect is produced by changing the following neurochemical systems:
- Synthesis of neurotransmitter. Drug increases or decreases the amount of neurotransmitters produced.
- Neurotransmitter transport. The drug interferes with the delivery of neurotransmitter molecules to the nerve endings.
- The accumulation of neurotransmitter. The drug interferes with the accumulation of neurotransmitter in the vesicles of nerve endings
- Isolation of the neurotransmitter. The drug causes premature release of neurotransmitter molecules into the synapse.
- Disintegration of the neurotransmitter. The drug affects the breakdown of the neurotransmitter through enzymes.
- Reverse neurotransmitter uptake. The drug blocks the reverse absorption of the neurotransmitter into the nerve endings.
- Activation of the receptor. The drug activates the receptor through mimicry.
- Lock receptor The drug makes the receptor inert, blocking it.
In addition to mimicry, drugs can affect the transmission of nerve impulses in many other ways. Models of the mechanisms of this influence are shown in Table 3-1. Neurotransmitters are produced from less complex compounds, the so-called “source molecules.” The production of mediators usually occurs in the cellular body or nerve endings, and if this process goes on in the cellular body, then before the mediator can work, it must also be transported to the nerve ending. Some drugs interfere with the production or delivery of a mediator. Neurotransmitter molecules accumulate in small containers (bubbles) along the edges of nerve endings. Some drugs affect the ability of bubbles to accumulate the necessary substances. For example, under the influence of a drug, reserpine, which was once used to treat high pressure, leaks appear in the bubbles, and the neurotransmitters contained in them cannot reach the synapse in the right amount in time. Other drugs have the opposite effect, increasing the flow of mediators into the synapse.
This is how stimulants act, such as amphetamines.
Another important feature of the transmission of nerve impulses is that the neurotransmitters should be deactivated after exposure. A neuron can be compared with a rechargeable electric battery: after excitation, it needs recharging. But it begins after the keys are taken out of the locks. Deactivation of the neurotransmitter can be done in two ways: by fermentation (destruction by enzymes) and reverse absorption. Enzymes are special compounds responsible both for the production of neurotransmitters and for their destruction to the state of inert substances. These are very complex processes. There are many chemicals in the brain tissue, and they are constantly changing their structure. Consider the production and destruction of acetylcholine, one of the most important neurotransmitters. To obtain it, the enzyme acetyltransferase reacts with the “original” choline molecule. As a result of the destruction of acetylcholine, for which another enzyme, acetylcholinesterase, is needed, two metabolites, choline and acetate, are formed. (The names of enzymes necessarily contain the roots of the names of the substances with which the enzyme reacts, as well as the ending – ase.) The drug can interfere with the process of impulse transmission, affecting the enzyme. For example, some antidepressants interfere with the deactivation of the neurotransmitters norepinephrine, dopamine and serotonin, weakening the effect of monoamine oxidase, an enzyme that destroys these compounds.
The second way to remove neurotransmitters from the synapse is reverse absorption. Neurotransmitters return back to the nerve ending from which they were isolated. Such a decontamination process is more economical, since the neurotransmitter molecule remains intact and can be used again without spending energy on the development of new ones. Some drugs (especially cocaine and amphetamines) have one of their actions, blocking the process.
The last group of drug actions is directly on the receptor. Some drugs affect the receptor, posing as a real neurotransmitter (a kind of duplicate key that fits the lock). Other drugs wedge the lock and prevent the neuron from exciting. They are called blockers. In general, any substances, endogenous or not, that approach the receptor lock and activate the neuron, are called the protagonists of this receptor. Any compound that does not activate the neuron itself and prevents other substances from doing this is called an antagonist. For example, naloxone is an antagonist of receptors that are affected by opiates like heroin. If you give naloxone to a person who has just taken a lethal dose of heroin, he will not only not die, but will even come to such a state as if he had not taken the drug.
In general, naloxone completely blocks and repeals all effects of heroin and other opiates. Therefore, naloxone is called an opiate antagonist. It should be remembered that although drugs interact with brain tissue very differently, the mechanism of this interaction always contains processes characteristic of the normal functioning of the body. The drug activates or slows down the functioning of certain parts of the brain with certain natural functions. Differences in the action of different drugs can be explained by examining which neurotransmitters they influence and how. Therefore, it is necessary to consider the neurotransmitter systems of the human brain and some of their known functions.