Peripheral nervous system drugs acting

The rate-limiting step in the synthesis of the catecholamines from tyrosine is tyrosine hydroxylase, so that any drug or substance which can reduce the activity of this enzyme, for example by reducing the concentration of the tetrahydropteridine cofactor, will reduce the rate of synthesis of the catecholamines. Under normal conditions tyrosine hydroxylase is maximally active, which implies that the rate of synthesis of the catecholamines is not in any way dependent on the dietary precursor tyrosine. Catecholamine synthesis may be reduced by end product inhibition. This is a process whereby catecholamine present in the synaptic cleft, for example as a result of excessive nerve stimulation, will reduce the affinity of the pteridine cofactor for tyrosine hydroxylase and thereby reduce synthesis of the transmitter. The experimental drug alpha-methyl-para-tyrosine inhibits the rate-limiting step by acting as a false substrate for the enzyme, the net result being a reduction in the catecholamine concentrations in both the central and peripheral nervous systems. 

Analgesics are divided into two groups opioids (morphine-like substances), which predominantly influence the central nervous system (CNS) and nonopioids (nonsteroidal antiinflammatory or fever-reducing drugs—NSAID), which act predominantly on the peripheral nervous system. 

Opioid drugs act at opioid receptors distributed throughout the central/peripheral nervous system, causing a wide range of physiological, behavioural and cognitive effects. The main adverse drug interactions are due to additive depressive effects on the CNS, which results in loss of consciousness, respiratory depression and hypotension. 

We have been focusing on a microscopic view of the nervous system as we considered how drugs might act at the level of the single neuron. We now turn to the larger picture and consider a macroscopic view of the nervous system. The structure of the nervous system is outlined in Figure 3.3. The major distinction is between the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS... 

To illustrate this, we are going to concentrate on one particular field—cholinergic and anticholinergic drugs. These are drugs which act on the peripheral nervous system, and so it is important to have some idea of how that system works before we proceed. 

Clonidine reduces blood pressure by acting on the central nervous system, but it also contracts blood vessels in the peripheral nervous system, and this leads to an increase in blood pressure. The biological activity of a series of related compounds on the central nervous system was found to correlate with the partition coefficient between octanol and water and the biological activity on the peripheral nervous system. The study indicated that there was an optimum value for the partition coefficient, and that central and peripheral nervous system activity could not be separated, suggesting that to find a drug that only acts on the central nervous system it would be necessary to try compounds unrelated to clonidine. Clonidine attaches to the same type of receptor in both the central and peripheral nervous systems — hence the correlation between central and peripheral nervous system biological activity. To attach to the receptor in the central nervous system, however, it has to cross the blood-brain barrier and thus must dissolve in lipids to reach its target. This leads to the correlation of central nervous system activity with lipid solubility. 

Serotonin mediates many central and peripheral physiological functions, including contraction of smooth muscle, vasoconstriction, food intake, sleep, pain perception, and memory, a consequence of it acting on several distinct receptor types. Although 5-HT may be metabolized by monoamine oxidase, platelets and neurons possess a high-affinity mechanism for reuptake of 5-HT. This mechanism may be inhibited by the widely prescribed antidepressant drugs termed selective serotonin re-uptake inhibitors (SSRl), e.g. fluoxetine (Prozac ), thereby increasing levels of 5-HT in the central nervous system. 

---