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Acetylcholine is a neurotransmitter for both the peripheral nervous system (PNS) and the central nervous system (CNS). In the PNS acetylcholine is responsible for two functions, contraction of skeletal muscle and as a neurotransmitter in the autonomic nervous system. In the CNS acetylcholine, in conjunction with neurons, form a system of neurotransmitters known as the cholinergic system.

Synthesis of acetylcholine is facilitated by an enzyme choline acetyltransferase (CAT). CAT manufactures acetylcholine by binding the molecules choline and acetate in specific neurons. Acetate comes from acetyl coenzyme A (CoA). The sodium-choline cotransport facilitates the cholinergic nerves to take up the choline, due to its high affinity. Once formed the acetylcholine is transferred and stored in the synaptic vesicles. Synthesis of acetylcholine also occurs in the synaptic gap.

Release of acetylcholine is due to cholinergic nerve stimulation causing an action potential to be generated which travels along the axon until it reaches the pre-synaptic terminal. This action potential results in depolarisation of the terminal, and for the acetylcholine (chemical transmitter) which is stored in the synaptic vesicles to be released into the synaptic gap. The chemical transmitter then diffuses across the gap where it binds to postsynaptic cholinergic receptors, either nicotinic or muscarinic receptors. Nicotinic receptors are situated on the post ganglionic cell bodies and muscarinic receptors are located on effectors found on peripheral tissues such as the iris and sweat glands. This interaction will either cause an effector response or stimulation of post ganglionic fibres.

Degradation or inactivation of acetylcholine occurs in the synaptic gap by the anzyme acetylcholinesterase (AChE) which is also present and highly specific to acetylcholine. AChE inactivates acetylcholine neurotramsitter actions by neutralising and converting the acetylcholine back into choline and acetate molecules. The choline molecules are then recycled and transported to the presynaptic terminal where the enzyme CAT remanufactures acetylcholine from these choline molecules and acetate molecules.


Adrenergic agonists drugs have the same or similar effect on the sympathetic nervous system (SNS) to that of Adrenaline (epinephrine), Noradrenaline, Dopamine etc. This is why they are referred to as sympathomimetic agents. Sympathomimetic means mimic the effects of the sympathetic nervous system. Sympathomimetic agents have two mechanisms of action, direct and indirect acting.

Direct acting agonist drugs molecules are able to bind directly to postsynaptic adrenoceptors and trigger a response without involving the presynaptic terminal. They can be very selective by acting on either α or β receptors, but alternatively can be very specific to their sub types for example β1 receptors.

Binding to the α1 receptor (a Gq coupled receptor) causes activation of the enzyme Phospholipase C (PLC) and an increase in triphosphoinositol (IP3) which results in smooth muscle contraction. Noradrenaline is an example of an α1 agonist.

A selective adrenergic agonist binding to a α2 receptor (G protein coupled receptor) causes the enzyme adenylate cyclase to be inactivated and a reduction in cyclic adenosine monophosphate (cAMP) resulting in smooth muscle constriction and neurotramitter inhibition. An example of an α2 agonist is Epinephrine.

By binding to a β receptor, the opposite effect of an α2 receptor occurs, adenylate cyclase is activated and cAMP is increased the results are dependant of which β receptor the adrenergic agonist binds to; β1 causes cardiac muscle relaxation, an example of a β1 agonist is Noradrenaline, β2 results in smooth muscle relaxation, Salbutamol,is a β2 agonist and β3 causes enhanced lipolysis, Amibegron is a β3 agonist.

Indirect acting agonist drugs work by being transferred to the presynaptic terminal by the amine reuptake pump. This stimulates the release of the chemical transmitter noradrenaline (NA) from the synaptic vesicles. NA then interacts with the post synaptic adrenoceptor, inducing the response.


Sympatholitic means an antagonistic effect on the sympathetic nervous system. Direct acting sympatholitics have an higher affinity for the receptor than agonists and serve to block a response., hence the term blockers. Direct antagonists can also be selective for certain receptors or subtypes. Examples of antagonist drugs and the receptors they bind are; α1 - Alfuzosin, αs - Phentolamine, β1 - Metoprolol and β2 - Propranolol. Indirect antagonists agents serve to block adrenergic nerve transmission. It does this by either stopping the release of NA or reducing the NA store

The dose response curve is a graphical interpretation of statistical data of the relationship between a particular drug dose and its effect on receptors. The effect can be either a physiological or biochemical response. Dose and time will both have an effect on this response.

The graph usually represents the drug concentration on the X-axis and the response on the Y-axis, usually as a percentage of a full response. The graduated doses are then plotted against the particular percentage response of a full response. For example if a particular drug dose has a half maximum response that dose would be plotted against 50%. An effective dose that achieves a 50% response is known as ED50 , and an effective concentration that achieves 50% response is known as EC50.

A threshold response is the term used for the first percentage of response against dose recorded above zero. As the doses are plotted a curve appears starting at zero and moving through 100% (maximum effect). This then indicates the dose required in order to attain maximum response of a particular drug or can be used to prescribe a dose based on a certain percentage of effect required. Once the maximum response dose is achieved increasing the dose higher will have no increased effect.

Data displayed on a dose response curve is more effective for analysis when plotted using a logarithmic scale. This ensures data is plotted uniformly and with the use of a scientific calculator exact doses for a particular drug response can be achieved.

The response of a drug can be carried out on tissue that has been removed from an organism or on the whole organism itself. On individual tissue it is possible to test a response to a particular drug dose, but it is very difficult to measure the amount of response. Individual tissue trials are conducted in order to indicate a response to a drug dose, once a response has been achieved, trails are then performed on whole organisms in order to obtain receptor responses for a variety of drug doses.

In the presence of an agonist drug, the increase in the dose should see an increase in the response, as more of the agonist drug binds to receptors and stimulates more cell activity. This would be indicated by the drug response curve.

Antagonist drugs are categorised as either competitive (reversible), competitive (irreversible) and non-competitive. Competitive (irreversible) are rarely used due to the irreversible nature. Competitive (reversible) antagonists reduce the effect on agonist drugs as they both are competing for the binding site. To increase the effect of the agonist in this situation would mean increasing the dose. With non-competitive antagonists the agonist will bind to the binding site and cause the effect, but the antagonist will block the effect without binding to the receptor.

With competitive (reversible) antagonist a maximum response can still be achieved by increasing the dose of and agonist. However, with competitive (irreversible) and non-competitive antagonists a maximum response can never be achieved no matter how much the agonist response is increased.