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Newsgroups: alt.drugs,alt.psychoactives
Check this out for accuracy -- ignore spelling errors, i haven't bothered
to run it through a spell-checker yet, which should catch them...
If anyone has any suggestions of good introductions to neurpharm for the
"public" along the lines of Synder's book, i'd appreciate it.
MDMA Neuropharmacology
MDMA is primarily a seritonergic (5-HTergic) drug. Serotonin
(5-hydroxytrytamine, 5-HT) is one of the major neurotransmitters in the
brain, and is synthesized from tryptophan through the intermediate
5-hydroxytryptophan. It is synthesized in 5-HT neurons, and stored in
synaptic vesicles. These vesicles release their 5-HT into the synaptic
cleft in response to the firing of the 5-HT neurons. In the synaptic
cleft the 5-HT neurotransmitter excerts its action on both pre- and
post- synaptic receptor sites (sites on the 5-HT neuron itself, and on
the neuron which it is communicating with.) 5-HT is then taken back
into the 5-HT neuron via the synaptic membrane 5-HT transporter (aka
"reuptake pump"), where it is again stored in the synaptic vesicles.
5-HT is metabolized primarily by monoamine oxidase (MAO) into
5-hydroxyindileacetic acid (5-HIAA).
Serotonin is thought to be responsible for many psychological (and
physiological) states including mood and sleep. It has been particularly
associated with major depression and obsessive compulsive disorder, and
drugs to treat these disorders tend to effect 5-HT (although things are
not quite clear-cut).
MDMA blocks the reuptake of 5-HT, similarly to SSRI (serotonin
specific reuptake inhibiting) anti-depressants such as fluoxetine (Prozac),
sertraline, and paroxetine. Unlike those drugs, however, MDMA appears
to enter the neuron, either through passive diffusion or directly
through the reuptake transporter, and causes the release of 5-HT. This
release is calcium-independent (i.e. independent of the firing of the
5-HT neuron) and appears to come from cytoplasmic stores rather than
from synaptic vesicles. The released 5-HT then enters the synaptic cleft
through the 5-HT transporter. MDMA thus acts on 5-HT similarly to the way
amphetamines act on dopamine.
It is thought that this efflux of 5-HT into the synaptic cleft, and
the subsequent action of this 5-HT on pre- and post- synaptic binding
sites is central to MDMA's neuropharmacology. MDMA, however, has
micromolar potency for the serotonin 5-HT2, muscarinic M1, alpha-2 adrenergic
and histamine H1 receptors. Agonist (stimulation rather than blocking)
properties at the 5-HT2 receptor have been found to fairly universally be
associated with "classical" psychedelic drugs such as LSD, psilocybin and
mescaline. It is possible that some of MDMA's "psychedelic" effect occurs
because of interactions with this receptor. The alpha-2 adrenergic receptor
may be associated with some of the carciovascular effects of MDMA.
MDMA also releases dopamine which may be central to both its
psychological action and to its neurotoxicity in animal studies. Pre-
treatment of an animal with a drug which blocks dopamine release will
also block MDMA neurotoxicity. Also, serotonin specific releasing agents
which are non-dopaminergic have been synthesized and been found to be
devoid of MDMA's neurotoxicity in animals, they have also been found to
be devoid of MDMA's psychological effects. MDMA tends to indirectly