A5 Neuropharmacology

Question 1

What is excitatory and inhibitory neurotransmission?

Answer 1

Excitatory neurotransmitters excite the post synaptic neurone for periods ranging from a few milliseconds to many seconds, producing depolarisation that may be sufficient to trigger action potentials.

Some neurotransmitters have the opposite effect, they inhibit the formation of action potentials in the post synaptic neurone because the membrane potential becomes more negative when the neurotransmitter binds to the post-synaptic membrane. This hyper-polarisation makes it more difficult for the post synaptic neurone to reach the threshold potential and so nerve impulses are inhibited.

Question 2

How does neurotransmission work (6.5)?

Answer 2

Neurotransmitter is released into the pre-synaptic neurone when a depolarisation of the pre-synaptic neurone reaches the synapse. The neurotransmitter depolarises the post synaptic neurone by binding to receptors in its membrane.

Question 3

What are inhibitory neurotransmitters?

Answer 3

Small molecules that are inactivated by specific enzymes in the membrane of the post synaptic neurone.

Question 4

What is summation?

Answer 4

More than one pre-synaptic neurone can form a synapse with the same post-synaptic neurone. Usually a single release of excitatory neurotransmitter from one pre-synaptic neurone is insufficient to trigger an action potential. Either one pre-synaptic neurone must repeatedly release neurotransmitter, or several adjacent pre-synaptic neurones must release neurotransmitter more or less simultaneously. The additive effect from multiple releases of excitatory neurotransmitter is called summation.

Some pre-synaptic neurones release an inhibitory rather than an excitatory neurotransmitter. Summation involves combining the effects of excitatory and inhibitory neurotransmitters. Whether or not action potentials form in a post-synaptic neurone depends on the balance between the effects of the synapses that release excitatory and inhibitory neurotransmitters and therefore whether the threshold potential is reached. This integration of signals from many different sources is the basis of decision-making processes in the central nervous system.

Question 5

How do fast acting neurotransmitters work?

Answer 5

Neurotransmitters such as acetylcholine or the ones discussed before have all been fast acting neurotransmitters. The neurotransmitter crosses the synapse and binds to the receptors less than a millisecond after an action potential has arrived at the pre-synaptic membrane. The receptors are ion channels which open or close in response to the binding of the neurotransmitter, causing an almost immediate but very brief change in the post-synaptic membrane potential

Question 6

How do slow acting neurotransmitters work?

Answer 6

They are either called slow acting neurotransmitters or neuromodulators which take hundreds of milliseconds to have effects on the post synaptic neurone. They may diffuse through the surrounding fluid and effect groups of neurones. Noadrenaline/norepinephrine, dopamine and serotonin are slow acting neurotransmitters.

Slow acting neurotransmitters do not affect ion movement across post synaptic membranes directly, but instead cause the release of secondary messengers inside post synaptic neurones which set off sequences of intracellular processes that regulate fast synaptic transmission. Slow acting neurotransmitters can modulate fast synaptic transmission for relatively long periods of time

Question 7

What are some example of slow acting neurotransmitters?

Answer 7

Noadrenaline/norepinephrine, dopamine and serotonin are slow acting neurotransmitters.

Question 8

What is the difference between slow acting neurotransmitters and fast acting neurotransmitters?

Answer 8

Fast acting neurotransmitters go across the synapse and cause ion channels to open within milliseconds, whereas slow acting neurotransmitters take hundred of milliseconds to have an effect on the post synaptic neurone. Slow acting neurotransmitters also diffuse through the surrounding fluid and effect groups of neurones rather than just one.
Fast acting neurotransmitters affect ion movement, but slow acting neurotransmitters do not they cause the release of secondary messengers inside post synaptic neurones which set off sequences of intracellular processes that regulate fast synaptic transmission. Slow acting neurotransmitters can modulate fast synaptic transmission for relatively long periods of time.

Question 9

How are memory and slow acting neurotransmitters linked?

Answer 9

Slow acting neurotransmitters have a role in memory and learning. They cause the release of secondary messengers inside post synaptic neurones that can promote synaptic transmission by mechanisms. Such as an increase in the number of receptors in the post synaptic membrane or chemical modification of these receptors to increase the rate of ion movements when neurotransmitter binds.
The secondary messengers can persist for days and cause what is known as long-term potentiation (LTP). This may be central to the synaptic plasticity that is necessary for memory and learning. Even longer-term memories may be due to a remodelling of the synaptic connections between neurones.

Basically slow acting neurotransmitters release secondary messengers which then promote that pathway. So they might add extra receptors or they might chemically modify the receptors to increase ion movement when something does bind. Therefore by making more things trigger in this pathway it is linked to learning and the plasticity of the brain.

Question 10

What are psychoactive drugs?

Answer 10

Psychoactive drugs affect the brain by either increasing or decreasing post synaptic transmission. Some drugs are excitatory because they increase post synaptic transmission and some are inhibitory because they decrease it.
Examples of excitatory drugs:
- Nicotine, contained in cigarettes. Derived from Nicotiana tabacum.
- Cocaine extracted from the leaves of a Peruvian plant Erythroxylon coca.
- Amphetamines, which are a group of artificially synthesised compounds.

Examples of inhibitory drugs:

• Benzodiazepines, a group of compounds including Valium that are synthesised artificially.
• Alcohol in the form of ethanol.
• Tetrahydrocannabinol (THC) obtained from the leaves of the Cannabis sativa plant.

Question 11

What are endorphins and what are they used for?

Answer 11

Endorphins can be used as painkillers.
Pain receptors in the skin and other parts of the body detect stimuli such as the chemical substances in a bee’s sting, excessive heat or the puncturing of skin. These receptors are the endings of sensory neurones that convey impulses to the CNS. When impulses reach sensory areas of the cerebral cortex we experience the sensation of pain. Endorphins are oligopeptides that are secreted by the pituitary gland and act as natural painkillers, blocking feelings of pain. They bind to receptors in synapses in the pathways used in the perception of pain, inhibiting synaptic transmission and preventing the pain being felt.

Question 12

Where are endorphins secreted?

Answer 12

They are secreted by the pituitary gland as natural painkillers, they block the pain receptors on synapses.

Question 13

Give 3 examples of excitatory psychoactive drugs?

Answer 13

Examples of excitatory drugs:

• Nicotine, contained in cigarettes. Derived from Nicotiana tabacum.
• Cocaine extracted from the leaves of a Peruvian plant Erythroxylon coca.
• Amphetamines, which are a group of artificially synthesised compounds.

Question 14

Give 3 examples of inhibitory psychoactive drugs?

Answer 14

Examples of inhibitory drugs:

• Benzodiazepines, a group of compounds including Valium that are synthesised artificially.
• Alcohol in the form of ethanol.
• Tetrahydrocannabinol (THC) obtained from the leaves of the Cannabis sativa plant.

Question 15

How do anaesthetics work?

Answer 15

Anaesthetics act by interfering with neural transmission between areas of sensory perception and the CNS.

Anaesthetics cause a reversible loss of sensation in part or all of the body. Local anaesthetics cause an area of the body to become numb, for example the gums and teeth during a dental procedure.
Anaesthetics are chemically varied and work in a variety of ways. Many of them affect more than just the sense organs and can also inhibit signals to motor neurones and other parts of the nervous system so they should only be administered by highly trained medical practitioners.

Question 16

When is it good to have less anaesthetic?

Answer 16

In brain surgery for example, if someone is having a brain tumour removed then it is good for the patient to remain conscious so that the effects on the brain can be monitored.

Question 17

When is the risk highest of awareness with anaesthetic?

Answer 17

The risk of awareness is highest in operations such as emergency caesarean sections in which it is best for the mother and child for the dose of anaesthetic to be minimised, although in these procedures a spinal block is almost always now used rather than a general anaesthetic, so the patient is awake and breathing is normal, but pain sensation cannot get beyond the spinal chord.

Question 18

What is a spinal block?

Answer 18

A spinal block is one injection, that blocks any sensation beyond the spinal chord. They inject local anaesthetic into the subarachnoid space in the spinal chord, it is a fluid space. It means you can feel nothing below the middle of your body.

Question 19

Why do we test drugs?

Answer 19

You need to test drugs in order to ensure that 1) the side effects of the drug are minor enough for it to be considered safe and 2) to calculate the dose and route of administration.

Question 20

Problems with drug testing?

Answer 20

• There have been some trials of new treatments where the difference between the testing group and the placebo group have been so great that it seems unethical to deny the control group the treatment. It therefore seems reasonable to abandon the trials and introduce the drug immediately. But the danger of this is that harmful side effects may only then be discovered when large numbers of patients have been given the new drug.
• There have also been some cases where groups of patients have campaigned for a new drug to be introduced before it has been fully tested. This may be acceptable with terminal diseases such as AID or forms of heart disease where the patient may regard any level of risk acceptable given the certainty of death without treatment. It is unlikely to be acceptable with non-critical illnesses where the risks from using a drug that has not been fully tested are too great compared with the risks associated with the disease remaining untreated.

Question 21

What are stimulant drugs?

Answer 21

Stimulant drugs mimic the stimulation provided by the sympathetic nervous system.
They promote the activity of the nervous system. They make a person more alert, energetic and self-confident. They also increase heart rate, blood pressure, and body temperature. The effects of stimulant drugs match those of the sympathetic nervous system. This is because stimulant drugs act by a variety of mechanisms to make the body respond as though it had been naturally stimulated by the sympathetic nervous system.
Some mild stimulants are present in food and drinks, for example caffeine in tea and coffee and theobromine in chocolate. Doctors sometimes prescribe stronger stimulants to treat conditions such as clinical depression and narcolepsy. Stimulant drugs are also sometimes used against medical advice. Examples include cocaine, amphetamines and nicotine in cigarettes.

Question 22

Give an example of 2 stimulants?

Answer 22

Pramipexole mimics dopamine and binds to dopamine receptors in post-synaptic membranes at dopaminergic synapses. Whereas some drugs that mimic neurotransmitters are antagonists because they block synaptic transmission, pramipexole is an agonist because it has the same effects as dopamine when it binds. Pramipexole is used during the early stages of Parkinson’s disease to help reduce the effects of insufficient dopamine secretion that characterises this disease. It is also used sometimes as an antidepressant.

Cocaine also acts at synapses that use dopamine as a neurotransmitter. It binds to dopamine re-uptake transporters, which are membrane proteins that pump dopamine back into the pre-synaptic neurone. Because cocaine blocks these transporters, dopamine builds up in the synaptic cleft and the post-synaptic neurone is continually excited. Cocaine is therefore an excitatory psychoactive drug that gives feelings of euphoria that are not related to any particular activity.

Question 23

Give an example of 2 sedatives?

Answer 23

• Diazepam (Valium) binds to an allosteric site of GABA receptors in post-synaptic membranes. GABA is an inhibitory neurotransmitter and when it binds to a receptor a chlorine channel opens, causing hyperpolarisation of the post synaptic neurone by entry of chloride ions. When Diazepam is bound to the receptors chloride enters at an increased rate, inhibiting nerve impulses in the post-synaptic neurone. It is therefore a sedative and can reduce anxiety, panic attacks and insomnia, it is also sometimes used as a muscle relaxant.
• THC (Tetrahydrocannabinol) is present in cannabis. It binds to cannabinoid receptors in pre-synaptic neurones. Binding inhibits the release of neurotransmitters that cause excitation of post-synaptic neurones. THC is therefore an inhibitory psychoactive drug and a sedative. Cannabinoid receptors are found in synapses in various parts of the brain, including the cerebellum, hippocampus and cerebral hemispheres. The main effects of THC are disruption of psychomotor behaviour, short-term memory impairment, intoxication and stimulation of appetite.

Question 24

What is drug addiction?

Answer 24

The American Psychiatric Association has defined addiction as:
‘a chronically relapsing disorder that is characterised by three main elements, a compulsion to seek and take the drug, loss of control in limiting intake and emergence of a negative emotional state when access to the drug is prevented’.

Question 25

What can effect drug addiction?

Answer 25

• Genes, some people have a genetic disposition towards drug addiction. One example is the gene DRD2 which copes for the dopamine receptor protein. There are multiple alleles of this gene and a recent study showed that people with one or more copies of A1 consumed less alcohol than those homozygous for the A2 allele.
• The environment, peer pressure, poverty and social deprivation, traumatic life experiences and mental health problems all contribute.
• Many addictive drugs, including opiates, cocaine, nicotine and alcohol affect dopamine secreting synapses. Dopamine secretion is associated with feelings of well-being and pleasure. Addictive drugs cause prolonged periods with high dopamine levels in the brain. This is so attractive to the drug user they find it very difficult to abstain.