KETAMINE Ketamine’s Properties and Effect on Brain Development

OVERVIEW  Pharmacology of ketamine  Brief history  Effects of ketamine usage  Ketamine & neuronal degeneration in a rat brain

PHARMACOLOGY/HISTORY  Structurally related to phencyclidine (PCP)  Prevents the actions of excitatory amino acids, such as glutamate and aspartate.  Dissociative anesthetic first used during the Vietnam War  Currently still used for veterinary practices and with children  First choice for victims w/unknown medical histories  In recent years, drug users have discovered its hallucinogenic properties  Also used by sexual predators to incapacitate their victims

EFFECTS OF KETAMINE  Cardiovascular  Respiratory  Vision  Gastrointestinal  Immune system  Psychoactive

BRAIN DEGENERATION  Apoptosis (programmed cell death)  Origin of control mechanism still undetermined but stimulation of NMDA (N-methyl-D-aspartate) seems vital to the survival of developing nerve cells  Need right amount of NMDA situation for sufficient brain development  Negative effects for both over and under- stimulation of NMDA receptors:  Over-stimulation of NMDA receptors, known as excitatory neurotoxicity, is known to exacerbate neuronal damage  Not enough NMDA stimulation triggers apoptosis in an immature central nervous system

Table 2: The effect of ketamine on weight gain Table 1: The effect of ketamine on righting reflex

This table shows the effect of a single dose of ketamine on different parts of the brain.

This table shows the effect of multiple ketamine doses on different parts of the brain.

This table shows the effect of MK-801 doses during a 24 hour duration.

 Ketamine = Noncompetitive NMDA receptor antagonist  Obvious evidence that it causes neurological degeneration after prolonged exposure  Duration of NMDA receptor blockage appears crucial factor in triggering neuronal degeneration in the developing rat brain  However, results might not necessary mirror similar effects in humans due to interspecies variability (i.e. different duration of brain development)  Probable that the capability of the human brain can stand more damage than a rat brain BRAIN DEGENERATION (con’t)

DEGENERATION FROM KETAMINE Figure 1 Silver-cupric staining of brain slices from P7 rat treated with saline (a) or ketamine (b) Degenerating neurones (dark cells) are abundant in the brain of the rats treated with ketamine.

DISCUSSION/CONCLUSION  Ketamine has a balance of positive and negative effects  Excessive neuronal damage from apoptosis after 24 hours of prolonged exposure to ketamine  More research is necessary to reveal ketamine’s full effect on humans.

REFERENCES  Dikkes P, Hayashi H, Soriano SG. Repeated administration of ketamine may lead to neuronal degeneration in the developing rat brain. Paedriatric Anaesthesia 2002; 12:  Copeland J, Dillon P. The health and psycho- social consequences of ketamine use. The International Journal of Drug Policy 2005; 16: