Reading comprehension 101

You wrote:

Thanks for your opinion.

Mine is that you replied to belittle and attack.. as usual.

No. Kitten is going to move the farm to Manhattan. I'm told that there
is good pasture land there going cheap.

Is there anyone you don't hate, Jan? Except for the saints of alt med,
of course.

<snipped>

Gracias.  I understand that "allergic reaction."  There's only so much
any of us can stand.

Kitten

I didn't announce it.

It is noted...you are  *selective* with who harasses.

I'm not on *her* case; you and I were arguing. T1 hasn't even
participated in this part of the thread.

I totally agree. She does need help NOW. How am I supposed to get shoes
to her? I'm nowhere near NYC. If I lived there, I would advocate for
her in *person,* if she would let me, but I have 3 kids to take care
of. I can't just pick up and go to NYC.

I'd love to see her get what she wants and needs, but there's no way I
can get her a prescription for Dexedrine, and no way I can get her old
apartment back.

If she will see the SSI/SSDI process through and get some temporary,
transitional housing, she'll have a start on solving her problems. But
she's got to go fill out those applications herself, or contact the
advocacy group I posted to her. They would walk her through a lot of
that.

That's the kind of help *I* think she needs now. We see things
differently, but we both want a safe, secure, positive outcome for her.

Desipramine is a tricyclic antidepressant that inhibits the reuptake of
norepinephrine, and is sold under the brand names Norpramin and
Pertofrane. I believe it can be bought as a generic, and is probably
cheaper than Effexor (Venlafaxine), which is also supposed to become
available as a generic sometime this summer.

Effexor is a serotonin and norepinephrine reuptake inhibitor; it has a
different mechanism of action than Desipramine, but works well for the
symptoms you described, also. Effexor also treats anxiety, but
Desipramine might be a better choice if you have neuropathy (nerve
pain).

The TCAs (like Desipramine, Imipramine) and related meds tend to have
more unpleasant side-effects than the newer medications (bearing in
mind that any psychoactive drug will have side-effects at first), and
are not typically considered first-line anti-depressants any more.
That's not to say you can't get it, if you request it. You would have
to talk with a doctor.

It may take some time to determine which medication works best for you.
I know you've said you hate the experimentation, but sometimes it's
worth the discomfort and annoyance in the long run.

BTW, most drug manufacturers have programs that provide free medication
to people who can't afford them. If you go back to a doctor, be sure to
ask about this, because he/she will be able to help with the
application process (and possibly also provide free samples).

Tri-cyclics ARE safer and more effective then newer anti-depressants;
however,  given how unsafe and ineffective newer antidepressants all
are---that's not saying much.

An ASD-med poster, Larry Hoover,   (whose double depression was
misdiagnosed as bipolar disorder) obtained relief from most of the
symptoms you mention from SJW.

"Kira" appears to be the most reputable brand of SJW sold in the
US;however,  the brands Movana and Perika are given high marks too.

SJW is the first choice wrt mood brighteners in many European
countries.

Empirical studies:

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S98-102

Hyperforin--antidepressant activity by a novel mechanism of action.

Muller WE, Singer A, Wonnemann M.

Department of Pharmacology, University of Frankfurt, Frankfurt/M.,
Germany.

Hyperforin represents a major antidepressive constituent of St. John's
wort
(SJW) extract. It not only inhibits the neuronal uptake of serotonin,
norepinephrine and dopamine like many other antidepressants, but also
inhibits GABA and L-glutamate uptake. This broad-spectrum effect is
obtained
by an elevation of the intracellular Na+ concentration, probably due to

activation of sodium conductive pathways not yet finally identified but
most
likely ionic channels. This makes hyperforin the first member of a new
class
of compounds with a preclinical antidepressant profile due to a
completely
novel mechanism of action.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S89-97

Effects of Hypericum perforatum (St. John's wort) on passive avoidance
in
the rat: evaluation of potential neurochemical mechanisms underlying
its
antidepressant activity.

Misane I, Ogren SO.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Mis...@mail.em.mpg.de

Along with traditional pharmacotherapies, extracts of Hypericum
perforatum
L. (St. John's wort) are used in the treatment of mild to moderately
severe
depression. Hypericum is a nonspecific inhibitor of the neuronal uptake
of
monoamines (serotonin, 5-HT; noradrenaline, NA; dopamine, DA) as well
as
GABA and glutamate. Hypericum extracts have been shown to be active in
several different "animal models for antidepressant drugs". As one of a

large number of chemical constituents, the phoroglucinol derivative
hyperforin might be an important "antidepressant component" of
hypericum.
However, the exact role of neurochemical mechanisms underlying in vivo
actions of hypericum and hyperforin are not well defined. In the
present
study, we compared the effects of hypericum, hyperforin and
hyperforin-free
hypericum and the three conventional antidepressants paroxetine,
imipramine
and desipramine using the passive avoidance (PA) task in the rat. The
5-HT-releasing compound p-chloroamphetamine (PCA), which operates
through
the 5-HT neuronal transporter, was used to reveal the potential in vivo

effects on 5-HT uptake mechanisms. To examine the ability of the
test-compounds to enhance noradrenaline (NA) transmission in vivo,
subeffective doses of scopolamine were used. Taken together, our
results
suggest that (1) hypericum given at high doses can probably affect the
neuronal 5-HT uptake mechanisms in a manner more reminiscent of TCAs
than
SSRIs; (2) similar to TCAs and SSRIs, hypericum and hyperforin are
active in
the scopolamine test. Hyperforin appears to play a major role in the
action
of hypericum in this model. Both 5-HT and NA might concomitantly
contribute
to the effects of different antidepressants in the "low-dose
scopolamine"
model; (3) hypericum might enhance both 5-HT and NA transmission in
forebrain limbic brain circuits important for mood control, which could

underly its antidepressant effects. However, the relative contribution
of
different constituents and exact mechanisms of action require further
evaluation.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S61-9

Hypericum extract and hyperforin: memory-enhancing properties in
rodents.

Klusa V, Germane S, Noldner M, Chatterjee SS.

Department of Pharmacology, Faculty of Medicine, University of Latvia,
Riga.
vijak...@acad.latnet.lv

Effects of a Hypericum extract in therapeutic use and hyperforin sodium
salt
were evaluated in rat and mouse avoidance tests. In a conditioned
avoidance
response (CAR) test on the rat, oral daily administration of hyperforin

(1.25 mg/kg/day) or of the extract (50 mg/kg/day) before the training
sessions considerably improved learning ability from the second day
onwards
until the day 7. In addition, the memory of the learned responses
acquired
during 7 consecutive days of administration and training was largely
retained even after 9 days without further treatment or training. The
observations made using different doses indicate that these
learning-facilitating and/or memory-consolidating effects by the agents

follow inverse U-shaped dose-response curves in dose ranges lower than
(for
hyperforin) or equal to (for Hypericum extract) their effective dose in
the
behavioral despair test for antidepressants. In a passive avoidance
response
test on the mouse, a single oral dose (1.25 mg/kg) of hyperforin not
only
improved memory acquisition and consolidation, but also almost
completely
reversed scopolamine-induced amnesia. The single Hypericum extract dose

tested (25 mg/kg) did not reveal any significant effects in the passive

avoidance response (PAR) test on the mouse. These observations suggest
that
the Hypericum extract could be a novel type of antidepressant with
memory
enhancing properties, and indicate that hyperforin is involved in its
cognitive effects. Pure hyperforin seems to be a more potent
antidementia
agent than an antidepressant.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S42-4

A study of the antidepressant activity of Hypericum perforatum on
animal
models.

Gambarana C, Tolu PL, Masi F, Rinaldi M, Giachetti D, Morazzoni P, De
Montis
MG.

Department of Neuroscience, University of Siena, Italy.

The treatment of non-selected depressed patients with a hydro-alcoholic

extract of Hypericum perforatum has been reported to have an efficacy
similar to that of classical antidepressants. The effects of H.
perforatum
on three animal depression models have been studied: (a) an acute form
of
escape deficit (ED) induced by unavoidable stress; (b) a chronic model
of
ED, which can be maintained by the administration of mild stressors on
alternate days; (c) a model of anhedonia based on the finding that
repeated
stressors prevent the development of appetitive behavior induced by
vanilla
sugar in satiated rats fed ad libitum. H. perforatum: (i) acutely
protects
animals from the sequelae of unavoidable stress; (ii) reverts the
chronic
escape deficit state maintained by repeated stressors and (iii)
preserves
the animal's capacity to acquire motivated appetitive behavior.
Exposure to
chronic stress not only induces escape deficit, but also decreases
extraneuronal levels of dopamine in the nucleus accumbens shell; both
behavioral and neurochemical effects are reverted by long-term
treatment
with antidepressants. Three-week treatment with H. perforatum reverted
the
chronic stress effect on extraneuronal dopamine in the nucleus
accumbens. A
consistent body of data in the literature suggests that, among the
components of H. perforatum extract, hyperforin is the compound (or one
of
the compounds) responsible for the antidepressant activity. We compared
the
efficacy of the total extract with the efficacy of hyperforin after
p.o.
administration. In the acute-escape deficit model, hyperforin showed a
potency of about ten times that of the total extract in protecting rats
from
the sequelae of unavoidable stress. Thus, hyperforin appears to be the
most
likely active component responsible for the antidepressant activity of
H.
perforatum.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S29-37

Researching the antidepressant actions of Hypericum perforatum (St.
John's
wort) in animals and man.

Franklin M, Cowen PJ.

University of Oxford Department of Psychiatry, Warneford Hospital, UK.

We have studied the effect of acute and sub-chronic treatments of a
formulation of a methanolic extract of hypericum perforatum (HP, also
known
as St John's wort) on plasma hormones and brain neurotransmitters in
healthy
human volunteers and rats. Also studied were the effects of equivalent
acute
doses of two constituents of HP (with respect to LI 160 extract),
hypericin
and hyperforin in rats. In acute treatment studies in normal volunteers

subjects received 9 tablets of the finished product Jarsin 300 and
placebo
in the pilot study (unblinded) and in the main study (a double blind,
balanced order, cross-over design). Results in normal volunteer studies
show
that HP caused significant increases of salivary cortisol and plasma
growth
hormone (GH) whereas it decreased plasma prolactin versus placebo.
Plasma
hormone levels were associated with a rise in plasma hyperforin but not
with
hypericin, however no significant correlation was found. In the animal
studies, acute treatment with LI 160, hyperforin and hypericin all
caused
significant increases in plasma corticosterone. This was associated
with
significant increases in brain cortical tissue 5-HT content. The
corticosterone responses were attenuated by the 5-HT2 receptor
antagonist,
ketanserin but not by the 5-HT1A antagonist, WAY-100635. This suggests
that
the corticosterone responses may be mediated via a 5-HT2 mechanism of
action. When sub-chronic and acute treatment using two different doses
of LI
160 were compared, plasma corticosterone level were significantly
decreased.
Thus suggesting a down-regulation or desensitisation of post-synaptic
5-HT2
receptors. Plasma prolactin was significantly reduced by acute
treatment
with LI 160 and hyperforin treatment but not by hypericin. This was
associated with a concomitant rise in brain cortical tissue DA. Both LI
160
and hyperforin treatments decreased the plasma prolactin responses to
the DA
antagonist, haloperidol, suggesting that this may be associated with a
DA-mediated mechanisn of action. When acute and sub-chronic treatments
were
compared, plasma prolactin responses were increased in the
sub-chronically
treated animals. The studies when taken together suggest that the LI
160
extract may effect plasma hormonal changes via both 5-HT and
DA-mediated
mechanisms but do not involve noradrenaline (NA). The data also
suggests
that hyperforin may be more important than hypericin for effecting
these
changes following acute treatment. Further studies investigating both
acute
and sub-chronic effects of these compounds are necessary.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S22-5

Effects of hyperforin on the fluidity of brain membranes.

Eckert GP, Muller WE.

Department of Pharmacology, Biocenter Niederursel, University of
Frankfurt,
Frankfurt/Main, Germany.

Hyperforin, an acylphloroglucinol derivative isolated from Hypericum
perforatum (St. John's wort, SJW), affects several ionic conductance
mechanisms in brain cells by an as yet unknown mechanism. We tested the

effects of hyperforin on the fluidity of crude brain membranes from
young
guinea pigs. We performed fluidity measurements with three different
fluorescent probes. Diphenylhexatriene (DPH) and
trimethylammonium-diphenylhexatriene (TMA-DPH) anisotropy measurements
were
inversely correlated with the flexibility of fatty acids in the
membrane
hydrocarbon core and in the hydrophilic area of membrane phospholipids,
resp
ectively. The ratio of pyrene excimer to monomer fluorescence
intensities
was used as an indicator of membrane annular and bulk fluidity.
Incubation
of brain membranes with relatively high concentrations of hyperforin
sodium
salt (10 micromol/l) resulted in increased DPH and decreased TMA-DPH
anisotropy, respectively, indicating that hyperforin modifies specific
membrane structures in different ways. It decreases the flexibility of
fatty
acids in the membrane hydrocarbon core, but fluidizes the hydrophilic
region
of membrane phospholipids. Interestingly, relatively low concentrations
of
hyperforin (0.3 micromol/l) significantly decreased the annular
fluidity of
lipids close to membrane proteins. These findings are remarkable, as
inhibition of several neurotransmitter-uptake systems and modulation of

several ionic conductance mechanisms by hyperforin occur in the same
concentration range. However, bulk fluidity was unchanged by this low
hyperforin concentration. The results emphasise a physicochemical
interaction of hyperforin with specific membrane structures that
probably
contribute to its novel pharmacological properties.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S137-42

Neurochemical studies with St. John's wort in vitro.

Simmen U, Higelin J, Berger-Buter K, Schaffner W, Lundstrom K.

Institute of Pharmaceutical Biology, University of Basel, Witterswil,
Switzerland.

The effect of extracts and constituents of St. John's wort, Hypericum
perforatum, at various CNS receptors were studied by radioligand
binding
techniques in order to determine a profile of pharmacological activity
in
vitro. Binding inhibition was examined for the G-protein coupled
opioid,
serotonin (5-HT), histamine, neurokinin and corticotropin releasing
factor
(CRF) receptors, for the steroid estrogen-alpha receptor and for the
ligand-gated ionchannel GABA(A) receptor. Hypericin showed the most
potent
binding inhibiton of all tested constituents to human CRF1 receptor
with an
IC50 value of 300 nM. Preliminary GTPgamma35S binding studies to CRF1
coupled G-protein indicated an antagonistic action for hypericin. The
acylphloroglucinole hyperforin failed to inhibit 125I-astressin binding
to
hCRF, receptor up to 10 microM. Hyperforin inhibited binding to opioid
and
serotonin (5-HT) receptors at IC50 values between 0.4 and 3 microM,
while
hypericin and pseudohypericin inhibited with weaker potency. The
biflavonoid
I3,II8-biapigenin inhibited 3H-estradiol binding to the estrogen-alpha
receptor with an IC50 value of 1 microM. The inhibition of 3H-muscimol
binding to the GABA(A) receptor is likely to be exclusively due to GABA

present in the extract. We therefore hypothesize that additive or
synergistic actions of several ditsinct compounds may be responsible
for the
beneficial antidepressant effect of St. John's wort.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S119-26

Acute and chronic actions of a dry methanolic extract of Hypericum
perforatum and a hyperforin-rich extract on dopaminergic and
serotonergic
neurones in rat nucleus accumbens.

Rommelspacher H, Siemanowitz B, Mannel M.

Department of Clinical Neurobiology, Benjamin Franklin Hospital, Free
University, Berlin, Germany. hrom...@zedat.fu-berlin.de

Dry hydroalcoholic extract of Hypericum perforatum L. is effective in
the
treatment of mild-to-moderate depression. Neither the mechanism of
action
nor the component or components of the extract responsible are known to

date. In several in vitro and ex vivo models, the extract and
hyperforin,
one of its active components, cause changes similar to those of
tricyclic
antidepressants. Little is known about effects on a complex neuronal
system
relevant to antidepressant actions such as the mesolimbic system in the

brain. In animal models of depression, the levels of dopamine were
reduced
in the nucleus accumbens, which is an important part of the mesolimbic
system. These and other deficits were compensated by imipramine. We
investigated the actions of the methanolic Hypericum extract LI 160 and
a
hyperforin-rich research extract in the shell region of the nucleus
accumbens under in vivo conditions after acute administration, and
after
application repeated fourteen times. Both extracts induced an increase
of
dopamine (DA) and 5-hydroxytryptamine (5-HT) levels measured by in vivo

microdialysis. The dose-response curve followed an inverse U-shape.
Repeated
application caused a rapid tolerance of DA but not of 5-HT neurones.
Similar
changes were observed after acute and repeated applications of
imipramine.
Several lines of evidence have suggested other active components in the

Hypericum extract. The potency of hyperforin surpassed that of
imipramine in
the acute release of both DA and 5-HT by the nucleus accumbens. The
effect
of hyperforin correlated well with the inhibiting potency on
high-affinity
DA and 5-HT uptake. The missing effect of relatively high doses on DA
and
5-HT levels as found in dose-response experiments may be explained by
self-inhibition caused by the activation of autosomal receptors and by
the
inhibition by GABA. The inhibition of neuronal GABA transport occurs at

somewhat higher concentrations of hyperforin. In conclusion, the
findings
demonstrate an imipramine-like effect of methanolic Hypericum extract
LI 160
and of hyperforin on mesolimbic, dopaminergic and serotonergic neurones
in
acute and chronic experiments, which probably contributes to the
antidepressant action of the medication. The methanolic Hypericum
extract
contains active compounds other than hyperforin.

Pharmacopsychiatry 2001 Jul;34 Suppl 1:S11-9

Stimulation of glutamate, aspartate and gamma-aminobutyric acid release
from
synaptosomes by hyperforin.

Chatterjee SS, Biber A, Weibezahn C.

Research Department, Dr. Willmar Schwabe GmbH & Co., Karlsruhe,
Germany.

Hyperforin is one pharmacologically active constituent of the medicinal
herb
Hypericum perforatum. The mechanism of its antidepressant-like activity
is
currently considered to be the inhibition of synaptic reuptake of
neurotransmitters. Here, we will demonstrate that it also stimulates
the
release of glutamate from rat cortical synaptosomes, and that this
effect is
preceded by an increase in their free calcium [Ca2+]i levels. These
hyperforin-related effects were also observed in the absence of Ca2+ in
the
medium. Although we noted enhanced glutamate, aspartate and GABA
release
under the influence of hyperforin, the release of various other amino
acids
was not enhanced. In contrast, reserpine did not influence the release
of
any of the amino acids studied. Adding hyperforin to synaptosomal
suspension
decreased their pHi, which returned to basal levels under certain
incubation
conditions. It also prevented the generation of ATP-induced pH
gradients of
isolated synaptic vesicles, and preformed pH-gradients were reversed by
it.
We will discuss the implications of our studies in understanding the
mechanisms of hyperforin activity in relation to current findings on
its
pharmacological activity profile. Our observations suggest that
neurotransmitter release stimulation from synaptosomes and the
previously
reported reuptake inhibitory properties of hyperforin are consequences
of
its effects on synaptosomal ionic homeostasis, and that it is not a
reserpine-like agent.

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