Antipsychotic Drugs

Synaptic transmission relies on the synthesis, storage, release, and diffusion through the synaptic cleft of transmitters. We see acetylcholine synthesized from acetyl CoA, then the storage and release of Ach, and also the degradation. Once we have the transmitter in the cleft, depending on how long its there, the effect is greater or lesser. Norepinephrine is the same. We see DOPA forming to dopamine, stored, then release and chemical degradation (not shown) by MAO, also the norepinephrine can be picked up again. Also shown is GABA, formed from glutamine. GABA is especially in the CNS. Also we have peptides as neurotransmitters. This is where the pharmacology of the CNS plays. This is a difficult field because there is such a lack of specificity.


Sometimes when you go on the street you see people who are homeless, here in SF it is very common to see. You might think that person is a bum or something. From a pharmacological perspective though, most of those people are treated and the reason that they act like zombies is because of the lack of specificity of those drugs. Dr. Levy comes in and makes the drugs sound very good, but in fact its very bad. This is a field of pharmacology where specificity is lower than anywhere else.



Once you have a transmitter going through the synaptic cleft, it will have to bind to the receptor. Depending on what receptor we have, we have a specific mechanism. Here we have an example of a nicotinic receptor in the ganglia, which is mostly just a channel that can bind ACh. When this is bound the channel opens to give electrical activity. On the other hand, if you go to the post ganglionic nerve fiber terminal and find a muscarenic receptor, it still binds ACh but the mechanism is totally different. It relies on the interactions of several proteins, G proteins mediate it, then after you get this complex response, it opens different pathways. In this example they give the example of a K+ channel, if the potassium channel opens it will have an opposite effect from the Na channel. Sodium channel opening results in depolarization, resulting in firing of nerve fibers. But if the potassium channel is opened, it causes the nerve fiber to relax. This is an opposite effect! So how do we get one or the other? The body knows how to specifically stimulate certain nerves for a specific response, but if you inject or ingest some drug, the effects will be throughout the body and we can’t really target specific receptors.



This is a pharmacologist’s view of the CNS. The pharmacologist sees the nerve that conducts an impulse, the synthesis and storage of transmitters, the release of the transmitter and reuptake, then the signal transduction and pharmacological response. So when you see a drug, either now or later in your career, remember this figure and try to figure out where the drug fits in the outline of mechanisms. We will try to do that with regard to the drugs that are anti-psychotic.

Category: Pharmacology Notes