Psychomotor stimulants

Psychomotor stimulants are drugs that stimulate the central nervous system to increase motor activity and to produce euphoria, excitement, and a feeling of having lots of energy.

Unfortunately, some drugs of abuse, like methamphetamine or cocaine, belong to this class of substances. However, there are a few medications in this class that do have clinical applications so let’s go over those.To understand how psychomotor stimulants work, let’s zoom in on one of the synapses of the brain.

Normally electrical signals, or action potentials, travel down the axon to the axon terminal, where they trigger the release of chemical messengers, called neurotransmitters, from synaptic vesicles into the synapse.

The neurotransmitters travel across the synapse and bind to receptors on the postsynaptic neuron, where they give the cell a message.

After the neurotransmitters have done their job, they unbind from the receptors, and can: diffuse away, get degraded by enzymes, or get picked up by proteins and returned to their original release site in a process called reuptake.Psychomotor stimulants, in general, increase the release of certain neurotransmitters, but their biggest effect is blocking reuptake receptors on presynaptic axon terminals.

Both actions keep neurotransmitters - like dopamine, norepinephrine, and serotonin - in the synapse longer, and increases their effects.For example, increased concentrations of dopamine in the brain’s reward pathway, which includes the nucleus accumbens, ventral tegmentum, and prefrontal cortex, produce intense feelings of euphoria, pleasure, and the emotional “high” associated with psychomotor stimulants.The physical “high” or feeling of hyper-stimulation is caused by increased norepinephrine concentrations throughout the brain, which produces a variety of effects throughout the body like increased energy, constricted blood vessels, dilated pupils, increased body temperature, increased heart rate, and increased blood pressure.

And finally, higher levels of serotonin are associated with greater confidence and happiness, and decreased anxiety.Okay, for psychomotor stimulants with medical applications, let’s start with the popular methylxanthines.

We are all familiar with this class of medication since it includes caffeine and theophylline found in coffee and tea respectively.

Now both these substances cause a stimulatory effect by blocking receptors for adenosine, a chemical that has numerous effects in the body like decreasing heart rate, decreasing neuronal activity - triggering sleepiness, and dilating blood vessels.

Now, migraines and other headaches can be caused by increased adenosine levels in the brain, so caffeine is often combined with an NSAID or acetaminophen to treat them.

Theophylline, on the other hand, is used to treat respiratory disorders like COPD and asthma. It works by inhibiting the enzyme phosphodiesterase, or PDE, in the smooth muscles in the respiratory tract.

Normally phosphodiesterase converts cAMP into an inactive form called 5-AMP. By inhibiting this enzyme, we increase the level of cAMP within the cell, and trigger smooth muscle relaxation and bronchodilation.

An overdose of methylxanthines can cause anxiety, nausea, arrhythmia, and seizures, so watch your coffee intake!Another medication that can help you stay awake is Modafinil.

It’s mainly used to treat narcolepsy, a condition where the person can fall asleep at any moment of the day and has episodes of paralysis out of the blue - not cool, right?

Well, modafinil inhibits dopamine reuptake and increases the release of glutamate and histamine in the brain, all of which increases arousal.

Modafinil is sometimes used as a “cognitive enhancer” off-label, but there’s no research to support this claim.Okay, let’s move on to the next group of medication like amphetamines and methylphenidate which work by blocking the reuptake of dopamine and norepinephrine at the presynaptic neuron.

It’s the preferred treatment for attention deficit/hyperactivity disorder, or ADHD for short, because it helps improve focus and decreases the impulsivity common in people with this disorder.

It also doesn’t have major side effects, making it the preferred medication. Finally, we have cocaine, sometimes called coke, which is a powerful psychomotor stimulant that has been used for over a thousand years.

It’s main mechanism is to block reuptake of dopamine, norepinephrine, and serotonin. In modern times, it’s become a popular “party drug” because cocaine reduces inhibitions and creates a feeling of euphoria or pleasure.

It therefore has a strong potential for addiction and overdose. When taken, cocaine can cause lapses in judgement, hypertension, dilated pupils, hallucinations, and most importantly, sudden cardiac death.Due to this, cocaine is only used topically in the clinical setting as a local anesthetic.

It works by blocking the Na+ channels on the membrane of neurons, which inhibits depolarization and the firing of action potentials during the transmission of pain signals.It also causes local vasoconstriction, which is handy since it’s used during small nasal surgeries to anesthetize and prevent excessive bleeding.Okay, here’s a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharmacology facts!

So, since coffee is the most popular psychomotor stimulant, let’s use a coffee shop as the scene. Outside the shop, let’s have our methylxanthines sitting at a table.

There’s a girl with a throbbing headache. She’s trying to cure it by drinking a huge cup of coffee to help you remember the indication for caffeine.Let’s have Aladdin as the waiter, bringing her more coffee since blocking adenosine is the main mechanism.

On the opposite side of the table is Socrates, the philosopher who represents theophylline. A cop using an asthma inhaler represent COPD and asthma, and he’s about to arrest Socrates for his radical ideas.

He has the letters “PD” on his vest for “police department”, but it also serves as a reminder that the mechanism of action is the inhibition of PDE, or phosphodiesterase.

Now, if we imagine the coffee shop as the presynaptic neuron, the door leading inside will represent the reuptake channels that take in released neurotransmitters.

So let’s have a supermodel, for modafinil, and she’s heading towards the door. Now, since this medication inhibits dopamine reuptake, let’s have her doberman trying to go into the shop, even though there’s a “no pets” sign on the door.

At the same time, her pet snake snuck out of her purse and is fleeing with a bottle of glue, since modafinil increases glutamate and hissstamine release.

The model’s boyfriend is sleeping on the ground in his PJs to represent narcolepsy, the main indication for this drug. By the otherside of the door, let’s have two dolphins on a date for methylphenidate.

One of them is carrying a model of a greek amphitheater for amphetamines. Their pet doberman for dopamine, is munching on a box of french fries, for norepinephrine.

The dog and it’s outside food is not allowed inside due to help you remember the reuptake inhibition caused by these drugs.

Their adopted son is very upset at this and he’s jumping up and down, acting all hyper, to represent ADHD. Okay, although the euphoric feeling caused by cocaine also comes from the reuptake inhibition of neurotransmitters, we are interested in it’s Na+ channel blocking properties.

So let’s put a couple of salt shakers and “Cocaine Cola” bottles at the display window. An elephant who recently got a nose job has a large band-aid on the tip of its truncated trunk.

He’s looking at the display to help you remember cocaine is mainly used as a local anesthetic for procedures like nasal surgeries.

##SummaryAll right, as a quick recap... psychomotor stimulants are medications that stimulate the central nervous system.

Some of these, like modafinil, methylphenidate, and cocaine work by increasing the amount of dopamine, norepinephrine, and serotonin in the synapse by preventing their reuptake.

Others, like the methylxanthines, block the action of adenosine, which normally decreases neuronal activity and causes drowsiness.

Some of these medications are used because they also have other useful mechanisms. For example, cocaine blocks Na+ channels and is used as a local anesthetic, while theophylline inhibits phosphodiesterase and is used as a bronchodilator.

map with all the mnemonics from the video Go ahead and pause the video so you can test yourself to see what you remember Stay tuned for