The LXX-NNN nomenclature (as in LSD-25) was used only by Albert
Hoffman and perhaps Sandoz.  LSD was the 25th compound synthesized by
Hoffman, hence its name.  The 23rd compound was actually LAE-23 or
lysergic acid ethyl-amide (a hydrogen replacing one of the ethyl groups
of LSD), not LMD-23, whatever that is.  Hoffman comments on the compound
in _LSD_My_Problem_Child_:

        "A substance very closely related to LSD, the monoethylamide
        of lysergic acid (LAE-23), in which an ethyl group is
        replaced by a hydrogen atom on the diethylamide residue of
        LSD, proved to be some ten times less psychoactive than LSD.
        The hallucinogenic effect of this substance is also
        qualitatively different: it is characterized by a narcotic
        component.  This narcotic effect is yet more pronounced in
        lysergic acid amide (LA-111), in which both ethyl groups of
        LSD are displaced by hydrogen atoms.  These effects, which I
        established in comparative self-experiments with LA-111 and
        LAE-32, were corroborated by subsequent clinical
        investigations.

        "Fif{*filter*} years later we encountered lysergic acid amide
        [LAE-23], which had been produced synthetically for these
        investigations, as a naturally occurring active principle of
        the Mexican magic drug ololiuhqui [and other related morning
        glories].

--
Ray Dueland

Hi.  I'm rather new to this operating system, and to news (in this form), so
forgive typeos, and let me know that I've succeded in posting.

Now, the question:  Ever heard of a drug called Katamine?  I may have the
spelling wrong, since I no longer have the source handy.  I was reading
Robert Anton Wilson's "Cosmic Trigger", which I generally found to be one of
the more ridiculous books I've read in a while.  However, there were a few
useful tidbits among all the tripe.  I'm just not sure how much of it I buy.
In there, somewhere, he mentions that John Lilly was messing around with a
psychadelic named Katamine...  I had never heard of it, but that doesn't mean
much.  ;-)
-------
-------------------------------------------------------------------------------

 The American University              |                  or


                                      |  UUCP: ...!psuvax!gallua.bitnet!kjcole
 Washington, D.C.                     |  CompuServe: 76167,1406
 (202) 651-5575                       |  The WELL:   kjcole
-------------------------------------------------------------------------------
  "The problem with opinions is that everyone's entitled to their own" - KJC

-------------------------------------------------------------------------------
Ref: Goodman and Gilman's The Pharmacological Basis of Therapeutics 7th ed 1985
-------------------------------------------------------------------------------
DISSOCIATIVE ANESTHESIA (KETAMINE HYCROCHLORIDE)

  Some arylcycloalkylamines may induce a state of sedation, immobility,
amnesia, and marked analgesia.  The name dissociative anesthesia is derived from
the strong feeling of dissociation from the environment that is experienced by
the subject to whom the agent is administered.  This condition is similar to
neurolept analgesia but results from the administration of a single drug.
  Phencyclidine was the first drug used for this purpose, but frequent
occurrence of unpleasant hallucinations and psychological problems soon led to
its abandonment.  These effects are much less frequent with ketamine
hydrochloride (2-[o-chlorophenyl]-2-[methylamino] cyclohexanone hyrdochloride;
KETALAR).
  Ketamine hyrdochloride is supplied in solution for intravenous or
intramuscular use in vials containing 10, 50, or 100 mg of ketamine base per
milliliter.
  Clinical Use.  For the induction of dissociative anesthesia in an {*filter*},
ketamine hydrochloride is administered in a dose of 1 to 2 mg/kg over a
period of about 1 minute.  (A similar induction follows the intramuscular
injection of 6 to 13 mg/kg.)  A sensation of dissociation is noticed within
15 seconds, and unconsciousness becomes apparent within another 30 seconds.
Intense analgesia and amnesia are established repidly.  Following a single
dose, unconsciousness lasts for 10 to 15 minutes and analgesia persists for
some 40 minutes; amnesia may be evident for a period of 1 to 2 hours following
the initial injection.  If anesthesia of longer duration is necessary,
supplementary doses of about one third or one half of the initial amount may
be administered.
  Muscular relaxation is poor, muscle tone may be increased, purposeless
movements sometimes occur, and occasionally {*filter*} and irrational responses
to stimuli are observed.  A soothing and quiet environment is necessary for
success with this technic.
  Hypoxic or hypercarbic stimulation of respiration is not seriously affected
following usual doses of ketamine.  Pharyngeal and laryngeal reflexes are
retained, and, while the cough reflex is depressed, airway obstruction does
not normally occur.  Airway resistance is in fact decreased, and bronchospasm
may be abolished.  Arterial {*filter*} pressure increases by as much as 25% and
cardiac output and rate increase.  When myocardial tissue is exposed to
ketamine in vitro, depression of contractility occurs.  The stimulation
observed in vivo is attributed to increased sympathetic activity.  When
ketamine is used to induce anesthesia in hypovolemic patients, hypotension
may occur, but the incidence is less than when inhalation agents are used.
Cerebral {*filter*} flow, metabolic rate, and intracranial pressure are augmented.
  Recovery.  Unlike the conventional intravenous agents, ketamine does not act
primarily on the reticular activating system in the brain stem; rather, it
acts on the cortex and the limbic system.  Perhaps this is the reason that
recovery after ketamine has some unusal features.  Awakening often requires
several hours and is not infrequently characterized by disagreeable dreams and
even hallucinations.  Sometimes these unpleasant occurrences may recur days or
weeks later.  Almost half of {*filter*}s over the age of 30 years exhibit delerium
or e{*filter*}ment, or experience visual disturbances.  The incidence of such
adverse psychological experiences is greatly reduced in children and young
{*filter*}s.  It is thought that the incidence of such unpleasant effects can be
lowered by the prior administration of morphine and scopolamine and by the
substitution of diazepam or thiopental for the last dose of ketamine.
  Status.  Ketamine hydrochloride is not indicated for patients with
hypertension or psychiatric disorders.  Intraocular pressure is increased with
ketamine and, therefore, its use is not advisable for many types of eye
surgery.  It can be employed for indiction of anesthesia, or, in combination
with nitrous oxide, to produce adequate general anesthesia.
  Ketamine is especially useful in children for the management of minor
surgical or diagnostic procedures or for repeated procedures that require
intense analgesia, such as changing burn dressings.  When the burns involve
the face and neck, the maintenance of an unobstructed airway with ketamine
makes it a valuable agent.
------------------------------------------------------------------------------
My previous posting on this subject was based on Anesthesia and the Brain by
John D. Michenfelder, M.D., Professor of Anesthesiology, Mayo Clinic and Mayo
Medical School, Rochester, Minnesota, 1988.  Curiously, Dr. Michenfelder says:

"Ketamine . . . was introduced as a general anesthetic in 1957 but never
received approval for human use (although it is commonly used in animals).
Failure to gain approval for human use was because of the high incidence of
convulsions as well as the occurence of psychotic reactions with vivid
hallucinations during emergence from the anesthetic effects."

"In cats, Kayama showed that ketamine, 3.5 mg/kg, stimulated cortical activity
but that this effect could be blocked by destruction of the mesencephalic
reticular formation.  Accordingly, it was concluded that ketamine acts via
the ascending reticular activating system."

MICHENFELDER and GOODMAN/GILMAN APPEAR TO DISAGREE ON BOTH OF THESE POINTS.  
DOES ANYONE HAVE AN EXPLANATION FOR THIS DISAGREEMENT?  (1) KETAMINE IS/IS
NOT APPROVED FOR USE IN HUMAN SUBJECTS?  (2) KETAMINE ACTS VIA THE ASCENDING
RETICULAR ACTIVATING SYSTEM?  CAN BOTH REFERENCES BE CORRECT?  IF SO, HOW?
------------------------------------------------------------------------------
My own observations of the effect of ketamine on the affective state of rats,
rabbits, and monkeys would lead me to be very reluctant to even attempt use
in human subjects.  Such animals exhibit markedly changed behavior for many
days after ketamine anesthesia.  However, I would be very interested in more
information about the extent of clinical use of ketamine in humans today.  I
would also be very interested in personal accounts of ketamine experiences
in non clinical settings (including dose, method of administration, onset of
effects, emergence phenonema, personality changes, and delayed after effects).

Neuroscience Program
Hedco Neuroscience Building, Room 534A
University of Southern California
University Park
Los Angeles, CA 90089-2520
------------------------------------------------------------------------------

Ketamine has been approved for use in humans for almost 20 years.
The drug was recently discussed in alt.{*filter*}.

--
Steve Dyer