What the Heck is Versed and Why does it Induce Amnesia?

You may have at some time, during a surgical procedure, had the whole thing done, and not have any memory of it. If so, you may thank a little compound used in combination with the analgesia/anesthesia called "Versed" or more properly, Midazolam.

"Midazolam

Medical

mi·daz·o·lam

A colorless crystalline derivative of diazepam with sedative and anxiolytic properties, usually used in its hydrochloride form as an intravenous anesthetic.."

For the more chemically minded, here is a bit about the structure.of this substance
http://web1.caryacademy.org/chemistry/rushin/

Structure

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Midazolam hydrochloride is a benzodiazepine which is usually administered intravenously for sedation. The chemical name is 8- chloro- 6- (2- fluorophenyl)-1 methyl- 4H- imidizo [1,5- a] [1,4] benzodiazepine hydrochloride; the empirical formula is C₁₈H₁₄Cl₂FN₃-HCl; the molecular weight is 362.25. At a pH of 5 or less, benzodiazepine ring is open and the molecule is water-soluble. On reaching pH 7.4 (in human blood), the ring closes and it becomes fat soluble.

Versed belongs to a group of compounds called "Benzodiazepines". Those more well versed (no pun)
in drugs, may be aware of something called "Valium", also known as "diazepam" (note the similarity with the benzoDIAZEPines word).

"Some sedative-hypnotic drugs produce marked anterograde amnesia. Drugs in the benzodiazepine family (including midazolam, ‘Versed’) and the alkylphenol class (propofol, ‘Diprivan’) produce profound amnesia when given in low concentrations to conscious subjects, while barbiturates (thiopental) and opioids (fentanyl) do not. We have studied midazolam and propofol using several different functional imaging techniques (recording the scalp electroencephalogram: EEG, functional magnetic resonance imaging: MRI, and measurement of cerebral blood flow using positron emission tomography: PET) to localize the neuroanatomical substrate of drug-induced amnesia. During drug administration in awake subjects, EEG beta power increases dramatically over frontal and central cortex while alpha activity decreases. These EEG changes correlate with dose-dependent decreases in verbal memory. Functional MRI scanning in single subjects has established that the neural transmission of primary sensory information to cortex is preserved during sedative drug administration. PET studies with ¹⁵O in subjects who received low or high doses of midazolam or propofol indicate that regional cerebral blood flow (rCBF) changes over the anterior brain in a dose-dependent fashion. Before drug, subjects asked to learn words showed increased rCBF in the left prefrontal cortex when compared to an auditory control condition (nonsense syllables). After propofol, this activation was abolished, coincident with severely impaired recall and recognition. The left prefrontal cortex has been identified as an area involved in verbal encoding. Neural activity in this area may be selectively decreased by certain sedative agents, resulting in reversible drug-induced amnesia."

It is clear then, that not ALL benzodiazepines, and not all substances which bind to the benzodiapine receptors (such as nicotinamide / vitamin B3 ) result in retrograde amnesia.
Valium, for example, is not known for this.

What then is more about the mechanism by which Versed is able to induce such amnesia?

"179 A Unitary Physiologic Theory for the Mechanism of Anesthetic-Induced Unconsciousness M.T.Alkire <malkire@uci.edu> (University of California, Irvine Medical Center, Department of Anesthesiology, Blg 53, Route 81-A, 101 City Drive South, Orange, CA 92868), R.Haier, J.Fallon.
A unifying theory of general anesthetic-induced unconsciousness must explain the common mechanism through which various anesthetic agents produce unconsciousness. Recently, functional brain imaging data obtained from volunteers during general anesthetic-induced unconsciousness demonstrated specific suppression of regional thalamic and midbrain reticular formation activity across two different commonly used volatile agents (Alkire, et. al., 2000) . The regions identified during the volatile agent study showed remarkable overlap with the regions identified during a similar imaging study investigating the effects of the intravenous anesthetic agent propofol on human consciousness (Fiset, et. al., 1999) . Intersecting the regions identified in both studies revealed the thalamus to be a primary target site for the effects of anesthetics on human consciousness. Integrating these findings with known functional neuroanatomy has lead us to the hypothesis that the essential common neurophysiologic mechanism underlying anesthetic-induced unconsciousness is likely to be, as with sleep-induced unconsciousness, a hyperpolarization block of thalamocortical neurons. Thalamocortical cells have two primary modes of firing, tonic and burst. Onset of physiologic sleep switches these cells from a predominately tonic-firing pattern to a predominately burst-firing pattern . The change in firing pattern occurs coincident with changes in the EEG pattern from one of behavioral arousal (i.e., low voltage, fast activity) to one of slow wave sleep (i.e., spindle and delta wave oscillations, high voltage, slow activity) . Animal physiology studies show that the switch in thalamocortical cell firing and the change in the EEG oscillation pattern happens because the thalamocortical cells become hyperpolarized. This hyperpolarization establishes a block to the transmission of sensory information through the thalamus, which results in the cortex being functionally disconnected from outside sensory experience with the onset of sleep-induced unconsciousness . During sleep this hyperpolarization block develops because of a decrease in tonic excitation from brainstem arousal centers. We suggest that hyperpolarization of thalamocortical neurons and the transition of thalamocortical activity from tonic to burst firing is likely to be a general principle of anesthesia that occurs through different mechanisms with different anesthetic agents. Anesthetics can affect the activity within thalamocortical-corticothalamic loops and cause thalamocortical hyperpolarization, coincident with the loss of consciousness, by at least four possible mechanisms including: (1) direct cellular hyperpolarization , (2) inhibition of excitement (i.e., decreased glutamatergic, cholinergic and aminergic signaling), (3) enhancement of inhibition (i.e., increased GABAergic and glycinergic signaling), or (4) any combination of these. A model of anesthetic-induced unconsciousness has been introduced to explain how the plethora of effects anesthetics have on cellular functioning ultimately all converge on a single neuroanatomic/neurophysiologic system (Alkire, et. al., 2000) , thus providing for a unitary physiologic theory of narcosis related to consciousness."