ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY*****
Norton SA Ruze P
Kava dermopathy.
In: J Am Acad Dermatol (1994 Jul) 31(1):89-97
ISSN: 0190-9622
Kava is a psychoactive beverage used ceremonially for thousands of years
by
Pacific Islanders. Kava is made from the root of the pepper plant,
Piper
methysticum, found in Polynesia, Melanesia, and Micronesia. The beverage
is a
nonfermented depressant with complex neuropharmacologic properties
that causes a
tranquil state of intoxication. Kava also affects the skin, causing
a peculiar
scaly eruption. The cutaneous effects were first reported by members
of Captain
James Cook's Pacific expeditions, but they have never been described
in
dermatologic literature. Heavy kava drinkers acquire a reversible ichthyosiform
eruption, kava dermopathy. The cause is unknown but may relate to interference
with cholesterol metabolism. Today kava is used across the Pacific
in both
traditional ceremonies and informal social events. In Western nations,
kava is
sold as a relaxant by health food stores. This article explores the
history of
kava dermopathy from Cook's early reports to its presence today.
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****LANCET*****
Ruze P
Kava-induced dermopathy: a niacin deficiency?
In: Lancet (1990 Jun 16) 335(8703):1442-5
ISSN: 0140-6736
Heavy chronic consumption of kava (Piper methysticum) is associated
with a
pellagroid dermopathy that has been attributed to niacin deficiency.
Over 200
male kava drinkers in the Tonga Islands were interviewed and examined
regarding
the characteristic skin changes. A scaly rash suggestive of ichthyosis
and eye
irritation were present in some heavy kava drinkers. 29 kava drinkers
with
prominent skin changes were randomised to receive either 100 mg oral
nicotinamide or placebo daily for three weeks. Skin examinations and
photographs
showed clinical improvement in 5/15 of the nicotinamide group and 5/14
of the
placebo group. These data, along with history and physical examination
findings,
suggest that niacin deficiency is not responsible for the rash, which
is more
characteristic of an acquired ichthyosis.
Registry Numbers:
59-67-6 (Niacin)
98-92-0 (Niacinamide)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****ANNALES PHARMACEUTIQUES FRANCAISES*****
Koch M Plat M Mehri H Saillant JP Kornowski
H
[Total kawalactones and dihydro-5,6 kawalactones determinations in
kawa
preparations (Piper methysticum Forst; Piperaceae)]
Dosage des kawalactones totales et des dihydro-5,6 kawalactones dans
les
preparations de kawa (Piper methysticum Forst., Piperacees.
In: Ann Pharm Fr (1973 Feb) 31(2):133-8
ISSN: 0003-4509 (Published in French)
[No Abstract Available]
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****ARCHIVES INTERNATIONALES DE PHARMACODYNAMIE ET DE THERAPIE*****
Duffield PH Jamieson DD Duffield AM
Effect of aqueous and lipid-soluble extracts of kava on the conditioned
avoidance response in rats.
In: Arch Int Pharmacodyn Ther (1989 Sep-Oct) 301:81-90
ISSN: 0003-9780
The aqueous, pyrone-free extract from kava (Piper methysticum) and the
lipid-soluble extract (kava resin) were tested for their effect on
amphetamine-induced hypermotility in mice and on conditioned avoidance
response
behavior in rats in a shelf-jump apparatus. Both kava extracts reduced
amphetamine-induced hypermotility. Aqueous kava extract in i.p. doses
of 30
mg/kg to 500 mg/kg had no effect on conditioned avoidance responses.
At or below
100 mg/kg i.p. kava resin also failed to modify the number of conditioned
avoidance responses obtained. However, 125 mg/kg of resin significantly
reduced
the number of conditioned avoidance responses by 18%. Increasing the
dose of
kava to 150 mg/kg caused ataxia and sedation which was so marked that
a modified
protocol was necessary. Only a marginally greater effect on conditioned
avoidance response was obtained under these conditions. The effect
of kava
extract was slight compared to that of the standard antipsychotic drugs
chlorpromazine and haloperidol in our procedure.
Registry Numbers:
300-62-9 (Amphetamine)
50-53-3 (Chlorpromazine)
52-86-8 (Haloperidol)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
Jamieson DD Duffield PH Cheng D Duffield AM
Comparison of the central nervous system activity of the aqueous and
lipid
extract of kava (Piper methysticum).
In: Arch Int Pharmacodyn Ther (1989 Sep-Oct) 301:66-80
ISSN: 0003-9780
The central nervous activity of the aqueous extract of kava was examined
in
mice, and compared to the effect of the lipid-soluble extract. The
aqueous
extract caused a loss of spontaneous activity without loss of muscle
tone. No
hypnotic effect was seen, but some analgesia was produced. The anticonvulsant
effect against strychnine was very slight and there was no evidence
of local
anesthetic action. There was a slight anti-apomorphine effect and
tetrabenazine-induced ptosis was decreased. The lipid-soluble extract
(kava
resin) also decreased spontaneous motility, together with a marked
reduction of
motor control. Hypnosis, determined by loss of righting reflex, was
produced,
analgesia was marked, and a local anesthetic action evident. Kava resin
also
decreased apomorphine-induced hyperreactivity and partially reversed
tetrabenazine-induced ptosis. Kava resin produces a greater range of
pharmacological actions than the aqueous extract, and the latter is
orally
inactive in mice and rats. The pharmacological effects of kava ingestion
appear
to be due to the activity of the compounds present in the lipid-soluble
fraction.
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*****BIOMEDICAL AND ENVIRONMENTAL MASS SPECTROMETRY*****
Cheng D Lidgard RO Duffield PH Duffield AM
Brophy JJ
Identification by methane chemical ionization gas chromatography/mass
spectrometry of the products obtained by steam distillation and aqueous
acid
extraction of commercial Piper methysticum.
In: Biomed Environ Mass Spectrom (1988 Nov) 17(5):371-6
ISSN: 0887-6134
Bornyl cinnamate has been identified as a constituent of kava resin
and of the
steam distillate of Piper methysticum. 5- Hydroxydihydrokawain was
identified in
commercial samples of P. methysticum originating from Vanuatu provided
an
initial aqueous extraction was employed. Commercial preparations, and
fresh
samples of the root of this plant from Fiji, lacked this compound.
Two
previously described N-cinnamoyl pyrrolidine alkaloids were also observed
along
with stigmasterol in kava resin from Fiji and Vanuatu. The products
derived from
aqueous 2 M hydrochloric acid extraction of P. methysticum were determined
from
methane chemical ionization gas chromatography/mass spectrometry analysis
which
identified a series of hydroxylated compounds (15a-d) derived from
formal
decarbonylation of the parent kava lactones. The products (13a-c) of
dehydration
of these compounds were also observed. The efficiency of kava resin
extraction
from plant material by water (the traditional method of preparation
of the kava
beverage) was typically 5-10% of that recovered by direct extraction
with an
organic solvent.
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****EUROPEAN JOURNAL OF PHARMACOLOGY*****
Gleitz J Friese J Beile A Ameri A Peters T
Anticonvulsive action of (+/-)-kavain estimated from its properties
on
stimulated synaptosomes and Na+ channel receptor sites.
In: Eur J Pharmacol (1996 Nov 7) 315(1):89-97
ISSN: 0014-2999
Kava pyrones are constituents of the intoxicating pepper (Piper methysticum
Forst), which has been shown to be anticonvulsive. The question of
how the
excitability of neurons is affected was investigated by determining
the
interaction of (+/-)-kavain with epitopes (site 1, site 2) of voltage-dependent
Na+ channels and the action of (+/-)-kavain on 4-aminopyridine-stimulated
synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and
[3H]batrachotoxin were used for radioligand-binding assays performed
with
synaptosomal membranes. Gultamate released from 4-aminopyridine- stimulated
cerebrocortical synaptosomes and the cytosolic concentrations of Na+
and Ca2+
([Na+]i, [Ca+]i) were detected fluorometrically by using an enzyme-linked
assay,
sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively.
(+/-)-Kavain failed to compete with [3H]saxitoxin up to 400 mumol/l
but dose-
dependently suppressed binding of [3H]batrachotoxin with an IC50 value
of 88
mumol/l (Ki = 72 mumol/l) although displacement of [3H]batrachotoxin
was
restricted to 33% of control at 400 mumol/l (+/- )-kavain. In stimulated
synaptosomes, 5 mmol/l 4-aminopyridine provoked an increase in [Na+]i
and
[Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction
in
[3H]batrachotoxin binding, 400 mumol/l (+/-)-kavain suppressed the
increase in
[Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent
with the
increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate
release (rate: 38 pmol/s*mg protein) which was dose- dependently diminished
to
60% of control by 400 mumol/l (+/-)-kavain. KCl depolarization (40
mmol/l)
provoked an increase in [Ca2+]i and glutamate release almost identical
to the
responses elicited by 4- aminopyridine but 400 mumol/l (+/-)-kavain
suppressed
only the rate of glutamate release by 9% of control. The data suggest
an
interaction of (+/-)-kavain with voltage-dependent Na+ and Ca2+ channels,
thereby suppressing the 4-aminopyridine-induced increase in [Na+]i,
[Ca2+]i and
the release of endogenous glutamate.
Registry Numbers:
1635-33-2 (kavain)
35523-89-8 (Saxitoxin)
504-24-5 (4-Aminopyridine)
56-86-0 (Glutamic Acid)
7440-23-5 (Sodium)
7440-70-2 (Calcium)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
Backhauss C Krieglstein J
Extract of kava (Piper methysticum) and its methysticin constituents
protect
brain tissue against ischemic damage in rodents.
In: Eur J Pharmacol (1992 May 14) 215(2-3):265-9
ISSN: 0014-2999
The purpose of the present study was to test whether kava extract and
its
constituents kawain, dihydrokawain, methysticin, dihydromethysticin
and yangonin
provide protection against ischemic brain damage. To this end, we used
a model
of focal cerebral ischemia in mice and rats. Ischemia was induced by
microbipolar coagulation of the left middle cerebral artery (MCA).
To quantify
the size of the lesion in mice, the area of the infarct on the brain
surface was
assessed planimetrically 48 h after MCA occlusion by transcardial perfusion
of
carbon black. In the rat model infarct volume was determined 48 h after
MCA
occlusion by planimetric analysis and subsequent integration of the
infarct
areas on serial coronal slices. Compounds were administered i.p., except
the
kava extract, which was administered orally. The effects of the kava
extract and
its constituents were compared with those produced by the typical
anticonvulsant, memantine. The kava extract, methysticin and dihydromethysticin
produced effects similar to those of the reference substance memantine.
The kava
extract (150 mg/kg, 1 h before ischemia) diminished the infarct area
(P less
than 0.05) in mouse brains and the infarct volume (P less than 0.05)
in rat
brains. Methysticin, dihydromethysticin (both 10 and 30 mg/kg, 15 min
before
ischemia) and memantine (20 mg/kg, 30 min before ischemia) significantly
reduced
the infarct area in mouse brains. All other compounds failed to produce
a
beneficial effect on the infarct area in mouse brains. In conclusion,
the kava
extract exhibited neuroprotective activity, which was probably mediated
by its
constituents methysticin and dihydromethysticin.
Registry Numbers:
19982-08-2 (Memantine)
495-85-2 (methysticin)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****HAWAII MEDICAL JOURNAL*****
Hope BE Massey DG Fournier-Massey G
Hawaiian materia medica for asthma.
In: Hawaii Med J (1993 Jun) 52(6):160-6
ISSN: 0017-8594
A literature search and traditional narration determined that at least
58 herbs
with scientific names were commonly used by Hawaiians for asthma. Of
particular
note were Piper methysticum, solanum americanum, and Aleurites molucana
with
oral tradition singling out Sophora chrysophylla. These four therapeutic
agents,
especially Sophora, have scientific merit and warrant further investigation
because of the recent increase in asthma mortality, their potential
for improved
patient compliance, minimal of side effects, and the low cost.
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****JOURNAL OF CHROMATOGRAPHY*****
Duffield AM Jamieson DD Lidgard RO Duffield PH
Bourne DJ
Identification of some human urinary metabolites of the intoxicating
beverage
kava.
In: J Chromatogr (1989 Jul 28) 475:273-81
ISSN: 0021-9673
Methane chemical ionization (CI) gas chromatography-mass spectrometry
(GC-MS)
has been used to identify some of the human urinary metabolites of
the kava
lactones following ingestion of kava prepared by the traditional method
of
aqueous extraction of Piper methysticum. All seven major, and several
minor,
kava lactones were identified in human urine. Observed metabolic transformations
include the reduction of the 3,4-double bond and/or demethylation of
the
4-methoxyl group of the alpha-pyrone ring system. Demethylation of
the
12-methoxy substituent in yangonin (or alternatively hydroxylation
at C-12 of
desmethoxyyangonin) was also recognised. This product was isolated
by
high-performance liquid chromatographic analysis of crude urine extracts
and
characterised by methane CI GC-MS. In contrast to the situation prevailing
in
the rat no dihydroxylated metabolites of the kava lactones, or products
from
ring opening of the 2-pyrone ring system, were identified in human
urine. GC-MS
analysis of urine can be readily utilised to determine whether donors
have
recently consumed kava.
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****JOURNAL OF ETHNOPHARMACOLOGY*****
Locher CP Burch MT Mower HF Berestecky J Davis
H Van Poel B Lasure A
Vanden Berghe DA Vlietinck AJ
Anti-microbial activity and anti-complement activity of extracts obtained
from
selected Hawaiian medicinal plants.
In: J Ethnopharmacol (1995 Nov 17) 49(1):23-32
ISSN: 0378-8741
Selected plants having a history of use in Polynesian traditional medicine
for
the treatment of infectious disease were investigated for anti-viral,
anti-fungal and anti-bacterial activity in vitro. Extracts from Scaevola
sericea, Psychotria hawaiiensis, Pipturus albidus and Eugenia malaccensis
showed
selective anti-viral activity against Herpes Simplex Virus-1 and 2
and Vesicular
Stomatitis Virus. Aleurites moluccana extracts showed anti-bacterial
activity
against Staphylococcus aureus and Pseudomonas aeruginosa, while Pipturus
albidus
and Eugenia malaccensis extracts showed growth inhibition of Staphylococcus
aureus and Streptococcus pyogenes. Psychotria hawaiiensis and Solanum
niger
inhibited growth of the fungi Microsporum canis, Trichophyton rubrum
and
Epidermophyton floccosum, while Ipomoea sp., Pipturus albidus, Scaevola
sericea,
Eugenia malaccensis, Piper methysticum, Barringtonia asiatica and Adansonia
digitata extracts showed anti-fungal activity to a lesser extent. Eugenia
malaccensis was also found to inhibit the classical pathway of complement
suggesting that an immunological basis for its in vivo activity was
identified.
This study has confirmed some of the ethnobotanical reports of Hawaiian
medicinal plants having curative properties against infections using
biological
assays in vitro.
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
Singh YN
Kava: an overview.
In: J Ethnopharmacol (1992 Aug) 37(1):13-45
ISSN: 0378-8741
Since the first significant contact with Europeans in the 18th century,
the
Oceanic plant, Piper methysticum Forst. (Piperaceae) and the beverage
prepared
from it, both of which are called kava, have become familiar to much
of the
outside world through both the written and visual media. The ceremonial
preparation and consumption of the beverage are probably its most conspicuous
and spectacular features. Kava continues to occupy a central place
in everyday
life in the islands concerned, although its role has been somewhat
diminished by
time and outside influences. Despite the large body of literature on
kava--about
800 entries are listed in a recent bibliography by Singh (1986)--there
has been
no comprehensive review on the subject. Earlier contributions by Keller
and
Klohs (1963) and Shulgin (1973) were selective in treatment and dealt
primarily
with chemical and pharmacological aspects. The monograph by Steinmetz
(1960)
remains a standard reference but understandably some of the information
in it
has become dated. The attention of the reader is also drawn to two
excellent
additions to the recent kava literature, by Lebot and Cabalion (1988)
and
Brunton (1989), which are, although somewhat restricted in focus, are
very
significant contributions to the subject. The present review paper
provides an
updated and a multidisciplinary overview of the subject. It was prepared
on the
basis of the author's personal experience--he is a native of Fiji and
lived in
that country for about 30 years--as well as the relevant literature
listed in
the Singh (1986) bibliography and some more recent publications.
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY*****
Schmitz D Zhang CL Chatterjee SS Heinemann U
Effects of methysticin on three different models of seizure like events
studied
in rat hippocampal and entorhinal cortex slices.
In: Naunyn Schmiedebergs Arch Pharmacol (1995 Apr) 351(4):348-55
ISSN: 0028-1298
Methysticin is one of the constituents of Piper methysticum which possesses
anticonvulsant and neuroprotective properties. Its effects on different
in vitro
seizure models were tested using extracellular recordings in rat temporal
cortex
slices containing the hippocampus and the entorhinal cortex. Elevating
[K+]0
induced seizure-like events with tonic and clonic electrographic phases
in area
CA1. Lowering [Ca2+]0 caused recurrent seizure like episodes with large
negative
field potential shifts. Lowering Mg2+ induced short recurrent discharges
in area
CA3 and CA1 while ictaform events lasting for many seconds were induced
in the
subiculum, entorhinal and temporal neocortex. In the hippocampus the
activity
stayed stable over a number of hours. In contrast, the ictaform events
in the
subiculum, entorhinal and temporal cortex changed their characteristics
after
one to two hours to late recurrent discharges. In a concentration-range
from 10
to 100 microM methysticin reversibly blocked all these types of epileptiform
activity. Decreases in [Ca2+]0 and associated slow field potentials
evoked by
repetitive stimulation of the stratum radiatum or the alveus remained
almost
unaffected by methysticin. A paired pulse stimulus paradigm used to
test for
effects of methysticin on synaptically evoked transient field potentials
in
normal medium revealed interference with mechanisms involved in frequency
potentiation. While responses to alvear stimulation were largely unaffected,
the
responses to a paired pulse stimulus to stratum radiatum were depressed
over the
whole range of tested stimulus intervals. The findings suggest that
methysticin
has effects on different patterns of epileptiform activity possibly
by
interfering with processes responsible for frequency potentiation.
Registry Numbers:
495-85-2 (methysticin)
7439-95-4 (Magnesium)
7440-09-7 (Potassium)
7440-70-2 (Calcium)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****NEUROPHARMACOLOGY*****
Gleitz J Beile A Peters T
(+/-)-Kavain inhibits veratridine-activated voltage-dependent Na(+)-
channels in
synaptosomes prepared from rat cerebral cortex.
In: Neuropharmacology (1995 Sep) 34(9):1133-8
ISSN: 0028-3908
Kava pyrones are pharmacologically active compounds extracted from Piper
methysticum Forst. Because kava pyrones were characterized by their
anticonvulsive, analgesic and centrally muscle relaxing action, we
investigated
the influence of (+/-)-kavain, a synthetic kava pyrone, on
veratridine-stimulated increase in intrasynaptosomal Na+ concentration
([Na+]i)
of rat cerebrocortical synaptosomes. [Na+]i was measured spectrofluorometrically
employing SBFI as Na+ sensitive fluorescence dye. Veratridine (5 mumol/I)
enhanced basal [Na+]i 6.6- fold from 11.3 to 74.1 mmol/l Na+. Incubation
of
synaptosomes for 100 sec with (+/-)-kavain was sufficient to reduce
dose
dependently the stimulated increase of [Na+]i with an IC50 value of
86.0
mumol/l, and almost complete inhibition of Na(+)-channels was attained
with 400
mumol/l) reduced veratridine-elevated [Na+]i to 30.4% and 7.9% of control
whereas the centrally acting muscle relaxant mephenesin (400 mumol/l)
was
without any effect. Postapplication of 400 mumol/l (+/-)- kavain or
10 mumol/l
TTX immediately diminished veratridine-elevated [Na+]i to nearly basal
levels
with a half life time of 69.7 and 41.8 sec, respectively. To study
the influence
of (+/-)-kavain on non stimulated synaptosomes, an increase in [Na+]i
was
induced by 200 mumol/l ouabain, which enhanced [Na+]i hyperbolically
with an
initial rate of 18.4 mmol Na+/l min. Preincubation of synaptosomes
with 400
mumol/l (+/-)-kavain or 10 mumol/l TTX partly prevented Na(+)-influx
for both
compounds to the same extent of about 57% of control. The presented
data
indicate a fast and specific inhibition of voltage- dependent Na(+)-channels
by
(+/-)-kavain.
Registry Numbers:
1635-33-2 (kavain)
71-62-5 (Veratridine)
7440-23-5 (Sodium)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****NEUROPSYCHOBIOLOGY*****
Munte TF Heinze HJ Matzke M Steitz J
Effects of oxazepam and an extract of kava roots (Piper methysticum)
on
event-related potentials in a word recognition task.
In: Neuropsychobiology (1993) 27(1):46-53
ISSN: 0302-282X
Twelve healthy volunteers were tested in a double-blind crossover study
to
assess the effects of oxazepam and an extract of kava roots (Piper
methysticum)
on behavior and event-related potentials (ERPs) in a recognition memory
task.
The subjects' task was to identify within a list of visually presented
words
those that were shown for the first time and those that were being
repeated. The
repeated words were associated with an increased positivity beginning
approximately 250 ms poststimulus. Oxazepam led to a reduction of a
negative
component in the 250-500 ms range for both old and new words and to
a reduction
of the old/new difference in the ERP associated with a significantly
worse
recognition rate. Kava on the other hand showed a slightly increased
recognition
rate and a larger ERP difference between old and new words.
Registry Numbers:
604-75-1 (Oxazepam)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****PHARMACOLOGY AND TOXICOLOGY*****
Davies LP Drew CA Duffield P Johnston GA Jamieson
DD
Kava pyrones and resin: studies on GABAA, GABAB and benzodiazepine
binding sites
in rodent brain.
In: Pharmacol Toxicol (1992 Aug) 71(2):120-6
ISSN: 0901-9928
Kava, an intoxicating beverage prepared from the pepper plant Piper
methysticum,
is widely consumed by the indigenous peoples in the islands of the
South
Pacific. As the first of a series of studies on the neuropharmacological
interactions of kava with CNS receptors we tested purified pyrones
and kava
resin for activity on GABA and benzodiazepine binding sites in rat
and mouse
brain membranes. Only weak activity was observed on GABAA binding sites
in
washed synaptosomal membranes prepared from rat brain and this was
abolished by
extraction of the membranes with Triton X-100, suggesting that lipid
soluble
components were involved. No effects were observed on GABAB binding
sites in rat
brain membranes in vitro. Kava resin and pyrones exerted some weak
effects on
benzodiazepine binding in vitro but this did not correlate with pharmacological
activity. In addition, in ex vivo studies, no effects were observed
on
[3H]diazepam binding to brain membranes prepared from mice in which
selected
kava constituents were injected intraperitoneally, whereas similarly
administered diazepam (5 mg/kg) inhibited [3H]diazepam binding by greater
than
95%. Similar lack of activity was observed in in vivo binding studies;
injection
of kava resin failed to influence the CNS binding of the benzodiazepine-receptor
ligand [3H]Ro15-1788 injected into mice prior to sacrifice. The pharmacological
activities of kava resin and pyrones do not appear to be explained
by any
significant interaction with GABA or benzodiazepine binding sites.
Registry Numbers:
12794-10-4 (benzodiazepine)
56-12-2 (GABA)
78755-81-4 (Flumazenil)
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
*****PLANTA MEDICA*****
Gleitz J Beile A Wilkens P Ameri A Peters T
Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper
methysticum on human platelets.
In: Planta Med (1997 Feb) 63(1):27-30
ISSN: 0032-0943
(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum
Forst.
(Piperaceae), was investigated regarding its assumed antithrombotic
action on
human platelets which was deduced from its ability to suppress arachidonic
acid
(AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase
(COX) and thromboxane synthase (TXS) activity, the latter two effects
being
estimated from the generation of prostaglandin E2 (PGE2) and thromboxane
A2
(TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked
a 90%
aggregation of platelets, the release of 14 pmol ATP, and the formation
of
either 220 pg TXA2 or 43 pg PGE2, each parameter being related to 10(6)
platelets. An application of (+)- kavain 5 min before AA, dose-dependently
diminished aggregation, ATP- release, and the synthesis of TXA2 and
PGE2 with
IC50 values of 78, 115, 71, and 86 mumol/l, respectively. The similarity
of the
IC50 values suggest an inhibition of COX by (+)-kavain as primary target,
thus
suppressing the generation of TXA2 which induces aggregation of platelets
and
exocytosis of ATP by its binding on TXA2-receptors.
Registry Numbers:
EC 5.3.99.5 (Thromboxane Synthetase)
1635-33-2 (kavain)
363-24-6 (Dinoprostone)
57576-52-0 (Thromboxane A2)
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*****PSYCHOPHARMACOLOGY*****
Jussofie A Schmiz A Hiemke C
Kavapyrone enriched extract from Piper methysticum as modulator of
the GABA
binding site in different regions of rat brain.
In: Psychopharmacology (Berl) (1994 Dec) 116(4):469-74
ISSN: 0033-3158
Regional differences in the modulation of [3H] muscimol binding to GABAA
receptor complexes by kavapyrones, compounds of the rhizome of the
plant Piper
methysticum which possess sedative activity, were demonstrated using
membrane
fractions obtained from target brain centers of kavapyrone action:
hippocampus
(HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers
outside the main kavapyrone effects as frontal cortex (FC) and cerebellum
(CER).
The kava extract enhanced the binding of [3H] muscimol in a concentration-
dependent manner with maximal potentiation of 358% over control in
HIP followed
by AMY and MED (main target brain centers). Minimal stimulation was
observed in
CER followed by FC. In contrast, apart from CER, the potency of kavapyrones
was
similar in the brain areas investigated with EC50 values ranging between
200 and
300 microM kavapyrones. Scatchard analysis revealed that the observed
effects of
kavapyrones were due to an increase in the number of binding sites
(Bmax),
rather than to a change in affinity. At a kavapyrone concentration
of 500 microM
the order of enhancement in Bmax was HIP = AMY > MED > FC > CER. When
kavapyrones are included together with pentobarbital or HPO the two
classes of
compounds produced a more than additive, i.e., synergetic effect on
[3H]
muscimol binding. Our findings suggest that one way kavapyrones might
mediate
sedative effects in vivo is through effects on GABAA receptor binding.
Registry Numbers:
2763-96-4 (Muscimol)
439-14-5 (Diazepam)
76-74-4 (Pentobarbital)
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