Ketamine – use, depressant effects as well as side effects

Ketamine and ketamine therapy – An overview

The active ingredient ketamine is a painkiller and anesthetic. Currently, ketamine therapy is being talked about especially because of its fast, positive effect on depression.

The first drug with the new mechanism of action in this indication is the enantiomer esketamine.

The following article provides a comprehensive overview of the active ingredient ketamine, which is steadily gaining in importance today.

The indications of ketamine

Ketamine is used to induce and perform general anesthesia, possibly combined with hypnotics. It is also used as a supplement for regional anesthesia.

In emergency medicine, ketamine is used in analgesia and anesthesia. Other indications for the drug include treatment of therapy-resistant status asthmaticus and analgesia in intubated patients.

A nasal spray containing esketamine is also available for patients in the U.S. to treat treatment-resistant depression.

Unlike conventional antidepressants, the antidepressant effect of ketamine is noticeable after just a few days, making the active ingredient extremely suitable for use in acute bouts of depression.

Mode of application and effect of ketamine

On the German market, the active ingredient ketamine is available in the form of a solution for injection. Esketamine is also officially approved for use as a nasal spray in the U.S.

Ketamine is a chiral agent that acts noncompetitively antagonistically at the glutamatergic NMDA receptors.

When the concentration of ketamine is in the conventional clinical dose range, it affects a variety of cellular processes:

  • NMDA channels are blocked,
  • Hyperpolarization-activated cyclic nucleotide channels are blocked,
  • Nicotinic acetylcholine ion channels are blocked,
  • Agonism of delta and mu opioid and potentiation of opioid,
  • Influencing the cyclic guanosine monophosphate system,
  • Influencing the AMPA receptors,
  • Influencing the metabotropic glutamate receptors,
  • Reduction of cholinergic neuromodulation,
  • Increased release of dopamine, norepinephrine and neurosteroids.

In addition, ketamine not only blocks NMDA, but also affects a variety of intracellular neuronal processes.

Presumably, the hypnotic effects can be attributed to the immediate blockade of NMDA and HCN1 channels.

In contrast, the sustained antidepressant effect probably results from other effects, such as the activity-induced increase in structural synaptic connections.

Cellular function appears to be shaped by the analgesic effects of ketamine in both the long and short term.

The short-term analgesic effects are probably mediated mainly by opioid sensitization and aminergic nociception.

The long-term effect in the form of inhibition of neuropathic pain, on the other hand, can be attributed to initiation of cell signaling cascades and receptor-mediated action.

The antidepressant effect of ketamine

In low doses, the ketamine increases glutamate neurotransmission by increasing AMPA receptor expression and glutamate release.

This subsequently results in an increased release of BDNF, which in turn activates mTOR.

This causes increased synaptic protein expression, which intensifies the structural connectivity between neurons, especially in the prefrontal cortex.

The side effects of ketamine

Very common side effects include waking reactions, for example in the form of motor restlessness, dizziness, nightmares and particularly vivid dreams.

Besides this, there may be an increase in heart rate and blood pressure. In addition, different interactions with other drugs must also be considered.