[MUSIC] Okay, so we're going to talk about the pharmacology of the autonomic nervous system. Now, this pharmacology is rich. It is so rich that it is, it is what people throughout all medical disciplines use to treat a number of conditions. Most notably, we'll, we'll focus on cardiac conditions and glaucoma. So, but, let's start with the basics. So, in both situations, in both the sympathetic, the sympathetic system, which is right here, and the parasympathetic system, which is right here. The, there are, these are two chain systems, instead of, as in the motor system, the skeletal motor system, there's one motor neuron that goes and enervates a skeletal muscle. One neuron, that does it. But these get to the target by two neurons. The first neuron sits in the central nervous system. We call it the preganglionic motor neuron, and it contacts a autonomic, a motor neuron that sits an an autonomic ganglion. So this is a ganglionic neuron. This is a ganglion. And in both the case of the parasymptathetic preganglionic and the sympathetic preganglionic, they're both using acetylcholine. So is this motor neuron, the motor neuron that's going to skeletal muscle. So, all motor neurons, whatever their flavor, are going to use acetylcholine. And all motor neurons are going to, the post-synaptic target, whether it's the skeletal muscle or whether it's a ganglion cell, is going to express a nicotinic acetylcholine receptor. This is a fast ionotropic receptor. It's going to very instantly give a response. So, here's nicotinic acetylcholine receptor, the sympathetic preganglionic goes to a ganglionic neuron which expresses this nicotinic acetylcholine receptor. The parasympathetic preganglionic also goes to a ganglionic neuron that expresses a nicotinic acetylcholine receptor. And there, the two systems diverge. So, in the parasympathetic system, we, we stay with acetylcholine as our neuro, neurotransmitter. The post, the ganglionic neutron sends a post-ganglionic axon, this is an unmyelinated axon that goes to one of the three targets, smooth muscle, cardiac muscle, or gland. And it is going to release acetylcholine. Now there's a difference between the release of acetylcholine here, and the release of acetylcholine here. And the difference is that the targets always are expressing metabotropic, very slow, indirect receptors. These are muscarinic, as opposed to nicotinic. They're acetylcholine receptors, but they're of the muscarinic flavor, and we label them as M1 to M whatever. They're, they're, it's a growing family. Each of these targets is going to express a different muscarinic receptor. The effect is that, although this transmission here is fast, this transmission is slow. So autonomic effects, they take place but they take their sweet time. Now, in the sympathetic system, instead we've now switched, once we get to the ganglion, we switch to norepinephrine. So, norepinephrine is contained in the ganglionic neurons, and they send a an axon, and again, an unmyelinated post-ganglionic axon that enervates one of the three targets, smooth muscle, cardiac muscle, or gland. These receptors that receive the message of norepinephrine are also metabotropic, and so therefore, they are also slow. Again, the response will happen, but it will take its sweet time. And so the, these metabotropic receptors that are, receive information from norepinephrine are called adrenergic receptors. So, how do we, how do we treat things? We treat things by either imitating or blocking the post-ganglionic neurotransmitter. So for instance, if we want to imitate a parasympathetic effect, we're going to give a drug that acts like acetylcholine, that acts like acetylcholine at muscarinic receptors. If we want to stop a parasympathetic effect, we're going to block a muscarinic we're going to block that. So, things that act like them, like a neurotransmitter called agonists and things that block the effects of neurotransmitters are called antagonists. So for instance, if we wanted to decrease secretions. Secretions are a very parasympathetic effect. We secrete stuff because we're going to go and try and digest stuff. And so if we want to try and reduce secretions, we're going to try and block the effect of the muscarinic receptors. So, we're going to antagonize that muscarinic receptor. Now it, when we talk about hypertension, the biggest the, the, the group of drugs that we use, in general, to treat hyp, hyper, hypertension are called beta-blockers. They're beta-blockers because they block the beta version of the adrenergic receptors. There are alpha adrenergic receptors and beta adrenergic receptors. And so these are ones that are antagonists at the beta adrenergic receptors. Now, the final thing that I will mention is that whenever you use the parasympathetic system, the drugs that act on the parasympathetic system either to mimic it or to block it, they stay peripheral. They have no effect on the brain other than an indirect effect. They, it might make you feel dry, you'll get dry mouth, dry eyes, and that might make you, put you in a bad mood, but it's not a direct effect. They're not acting on the brain. In contrast, drugs that act on the sympathetic system tend to also have psychotropic effects, they also act in the central nervous system. So, many of these drugs will also have a a direct effect on mood or affect or motivation. [MUSIC]
