Sumatriptan

UNDER REVIEW (September 2016)

Mechanism of Action:

One of the serotonin (5-hydroxytryptamine, 5-HT1D) agonists or ‘triptans’ based on the structure of tryptamine. Mimics the action of 5-HT at these receptors to constrict dilated cerebral blood vessels (cranial and basilar arteries). It also inhibits transmission through the trigeminal nerve which probably accounts for its efficacy in treating cluster headaches.

Lecture and CAL materials:

Gabapentin

UNDER REVIEW (September 2016)

Mechanism of Action:

Gabapentin is similar in structure to the neurotransmitter GABA but is not believed to act on the same brain receptors. It was synthesised in the hope that it would be a useful antiepileptic but it has also found use in treating neuropathic pain. Its exact mechanism of action is unknown, but its therapeutic action on neuropathic pain is thought to involve voltage-gated N-type calcium ion channels. It is thought to bind to the α;2δ; sub-unit of the voltage-dependent calcium channel in the central nervous system.

Lecture and CAL materials:

Amitriptyline

UNDER REVIEW (April 2017)

Mechanism of Action:

Amitriptyline is an antidepressant drug from the tricyclic antidepressant group. Amitriptyline probably exerts its antidepressant effects by inhibiting both serotonin and noradrenaline reuptake. It also has analgesic properties which might relate to blocking of calcium channels in the pain pathway (ie non-antidepressant action).

Lecture and CAL materials:

Codeine

Mechanism of Action:

Opioid agonist: activates mu opioid recrptors (GPCRs). See morphine for mechanism of action. Codeine is a methylated form of morphine and requires to be demethylated to morphine in order to act at mu receptors. It has about one tenth the potency of morphine as an analgesic, but interestingly has similar potency to morphine when used as an anti-tussive. This implies the cough suppressant action may involve a different type of receptor.

Indications:

  • Moderate pain (often in combination with paracetamol)
  • Cough
  • Diarrhoea

Lecture and CAL materials: (under review)

Nitrous Oxide

UNDER REVIEW (September 2016)

Mechanism of Action:

Gaseous inhalation anaesthetic which can also be used as an analgesic (with oxygen: entonox = 50:50 mix). Nitrous oxide is a dissociative agent which causes euphoria and dizziness. The mechanism of action is not completely understood, but it is thought that the gas interacts with the plasma membranes of nerve cells in the brain and thus affects the communication among such cells at their synapses, resulting in anaesthesia. These membrane actions are presumed to disrupt the propagation of nerve impulses as a consequence of depressant actions at excitatory synapes (e.g. glutamatergic), or facilitatory actions at inhibitory (e.g. GABAergic) synapses within the CNS. Current evidence from neurophysiological patch clamp studies on neurones suggest that the GABAa receptor is probably the primary target for GAs, though exactly how nitrous oxide, or inert gases such as xenon, interact with the receptor complex and/or the nearby neuronal membrane remains to be established.

Lecture and CAL materials:

Morphine

Mechanism of action:

Morphine is an opioid, a mu (µ) opioid receptor agonist, which results in analgesia and a reduction in peristalsis (constipation), together with various other effects.

Indications:

  • Pain
  • Historically, but less relevant now, as a treatment for diarrhoea.

Opioids are agonists at mu (mu = µ, Greek m, m is for morphine), delta and kappa opioid receptors (ORs). The highest affinity of morphine is for the mu receptor. There is some evidence for subtypes (1 and 2) of mu ORs, although the functional significance of this remains to be confirmed. Opioid receptors are found on neurons in somatosensory cortex, thalamus, various other brain centres involved in the pain pathway – the spinal cord and also on nociceptive terminals in the periphery, to relieve pain by reducing the “pain” signal.

Naloxone is an opioid antagonist (high affinity for mu Rs) which is used to classify ORs as GPCR [Gi/Go] 7TM metabotropic receptors that are antagonized by naloxone. ACTION of opioid agonists on peripheral nociceptors and in the spinal cord & brain (CNS): increased K+ conductance, decreased Ca++ results in hyperpolarization and decreased neurotransmission at pre- and post-synaptic sites on neurons in the pain pathway. Overall effect is a reduction in pain sensation.

Lecture and CAL materials: (under review)

Paracetamol

Mechanism of Action:

Mechanism and exact site of action unknown – was thought to inhibit COX-1 and 2 in the CNS,and possibly in the peripheral nervous system, but it doesn’t (or at least not to anything like the extent of most NSAIDs). Possibly inhibits a COX-1 or COX-2 variant. Antipyretic analgesic – generally not considered to be an anti-inflammatory agent.

Lecture and CAL materials: