The Kebilsphere

NMDA antagonists are often refered to as dissociative anaesthetics. While this term does have some validity when applied to the most common NMDA blockers ketamine, phencyclidine, and dextromethorphan, these effects are only seen at high doses. These compounds do not have a regular dose-activity relationship. Rather, the effects of these drugs changes dramatically with dose. The following is a list of effects by weight. These are grouped into plateau’s, as the effects do not smoothly transition from one to another, and as dose increases, the effects are not so much intensified as changed qualitatively. This list of plateau’s is taken from Wikipedia - Non-medicinal Use of Dextromethorphan

First plateau: At a dosage of 1.5 to 2.5 mg/kg, effects include a sensation of alertness, stimulant effects such as restlessness, increased heartbeat, and increased body temperature, intensification of emotions, general euphoria, euphoria linked to music, alteration of sensations of gravity, loss of balance, slight intoxication, and for some users nausea.
Second plateau: At 2.5 to 7.5 mg/kg, effects include the same effects of the first plateau, with added choppy sensory input, entering a dreamlike state of consciousness, increasing detachment from outside world, a heavier “stoned” feeling than with first plateau, and/or closed-eye hallucinations.
Third plateau: At 7.5 to 15.0 mg/kg, effects include flanging of visual effects, difficulty recognizing people or objects, chaotic blindness, dreamlike vision, inability to comprehend language, abstract hallucinations, delayed reaction time, decision making impairment, feelings of peace and quiet, near complete loss of motor coordination, short term memory impairment, and/or feelings of rebirth.
Fourth plateau: At 15.0 mg/kg or more, an individual may experience a perceived loss of contact with their own body, changes in visual perception, out-of-body experiences, perceptions of contact with “superior,” supernatural, or other archetypal beings (ie. gods, aliens, vampires, etc.), other miscellaneous delusions, lack of movement or desire to move, rapid heart rate, complete blindness, increased hearing, and intensification of third plateau effects.

The reason these drugs can so completely disable a person is quite obvious when one stops to think about just where and how this class of drugs works.

In the brain, their is a cocktail of neurotransmitters, neuromodulators, and neurosteroids carrying signals from one neuron to the next. Most of the most familiar compounds - serotonin, norepinephrine, dopamine, acetylcholine, and histamine, have effects in many different parts of the brain. Often these compounds are localized to discrete populations in the brain. Glutamate is different. It is THE primary excitatory neurotransmittor. That is, it is THE MAJOR excitatory neurotransmitter. It is opposed by GABA, which is the primary inhibitory neurotrasmitter. GABA and glutamate together are responsible for about 80 to 90% of all chemical signalling in the brain. They can be thought of as carrying most of the ON/OFF signalling, whereas the other neurotransmitters act as neuromodulators, working to dampen or increase the activity of neural circuits. Of course, this is a gross simplification, but it goes to show how this class of drugs can have such a dramatic effect. Blocking the NMDA class of glutamate receptor is like turning down, or turning off, a large proportion of the excitory signals - it is like shutting off a quarter the brain circuits. No other drug that specifically targets a neurotransmitter receptor has such a large, wide ranging, and powerful effect on the human brain. But, again, it all depends on the dose.