Antidepressants - 1

The main thing that we must remember is that in the CNS you have pathways connecting the midbrain where stimuli trigger something that ends up being emotional behavior and is carried out to the more peripheral areas of the motor neuron system. Different neurotransmitters such as norepinephrine, serotonin or dopamine have been identified. So in addition to the classical transmitters like acetylcholine we have these dopamine and norepi and serotonin pathways that have been associated with specific CNS diseases, some emotional, and some resulting in extra-pyramidal symptoms such as Parkinson’s. In addition, we have the GABA receptors, which are also carrying chloride. So it is against this type of transmission that most of the drugs available are aimed. Specificity is a problem, if you aim at one receptor it doesn’t mean it will be the only one affected; this is a big problem.

Some things to remember when dealing with the different drugs for psychosis, depression, anxiety, or Parkinson’s (“if you get this, you’ll get the gist of it”):

PHENOTHIAZINES are anti-psychotics given for crazy people (schizophrenics), and work by blocking dopamine receptors so that the pathways are impaired. These drugs eliminate the positive behavior of the schizophrenic without really curing it (like a straight jacket). This is like inhibiting some expression of activity, the fact that there is such lack of specificity doesn’t mean that they are useless; they control the patient and they do not sedate the patient. They are not addictive. By interfering with dopamine transmission you can get extrapyramidal problems (Parkinsonian) because the dopamine transmission is involved with this.

The ANTIDEPRESSANTS (like Prozac) block the reuptake of norepinephrine and serotonin at the nerve terminal, thereby enhance the transmission of these neurotransmitters.

ANTI-ANXIETY DRUGS (like Valium) enhance the chloride channel associated with the GABA receptor.

The ANTI-PARKINSON’S DRUGS have neurological aims. In this case, we are trying to improve the dopamine transmission, just the opposite of the anti-psychotic drugs. That’s why sometimes when we give people a phenothiazide drug for antipsychotic reasons it induces Parkinsonian effects.

SUMMARY

• Anti-psychotic: dopamine receptor blockade

• Anti-depressant: norepinephrine and serotonin (NE/5HT) transmission enhanced by blocking reuptake (Prozac)

• Anti-anxiety: GABA receptor chloride channel enhancement (Valium)

• Anti-Parkinson’s: dopamine transmission activation

Category: Pharmacology Notes