Baclofen Forum vs Alkoholismus

Die Veröffentlichung von J.F.Cryan und K.Kaupmann Don`t worry "B" happy!: a role for GABA-B-receptors in anxiety and depression, Trends in Pharmacological Science, 2005 gibt zum Teil eine Antwort auf die Frage: Angst, was ist das?
Anbei das abstract und die erste Seite.
LG invorio

GABA, the main inhibitory neurotransmitter in the brain,
regulates many physiological and psychological processes.
Thus, dysfunction of the GABA system is
implicated in the pathophysiology of several neuropsychiatric
disorders, including anxiety and depression.
However, the role of GABAB receptors in behavioural
processes related to these disorders has not been
resolved. GABAB receptors are G-protein-coupled receptors
that function as heterodimers of GABAB(1) and
GABAB(2) subunits. In addition to highly selective
agonists and antagonists, novel GABAB receptor tools
have been developed recently to further assist elucidation
of the role of GABAB receptors in CNS function.
These include mice that lack functional GABAB receptors,
and novel positive modulators of the GABAB
receptor. In this review, we discuss evidence that points
to a role of GABAB receptors in anxiety and depression.
GABA is the main inhibitory neurotransmitter in the
brain and GABA-mediated neurotransmission regulates
many physiological and psychological processes. There are
two major classes of GABA receptors: ionotropic GABAA
(including GABAC) receptors and metabotropic GABAB
receptors [1–3]. In 1980, Bowery and colleagues were the
first to characterize pharmacologically metabotropic
GABAB receptors as receptors that are insensitive to the
GABAA receptor antagonist bicuculline [3]. Baclofen is a
selective agonist at GABAB receptors. Presynaptic GABAB
receptors modulate neurotransmitter release by depressing
Ca2C influx via voltage-activated Ca2C channels
(Figure 1) [3]. Such presynaptic inhibition at GABAergic
terminals is involved in the induction of long-term
potentiation [3]. Postsynaptic GABAB receptors are
coupled mainly to inwardly rectifying KC channels [4]
and mediate slow inhibitory postsynaptic potentials
(Figure 1) [3]. GABAB receptors are abundant in the
brain, where they are localized in many neuronal cell
types including interneuron populations and some glial
cells (Figure 1). High levels of expression of GABAB
receptors in the limbic system [5] indicate a role in
regulating emotional behaviour. In this review, we
summarize knowledge of the function of GABAB receptors
in the brain. In particular, we focus on the recent
development of novel pharmacological and genetic tools
that have advanced knowledge on the role of GABAB
receptors in emotional disorders such as anxiety and
depression.
GABAB receptors
The first GABAB receptor cDNAs were isolated in 1997 [6].
The identification of a second GABAB receptor protein
soon after led to the discovery that native GABAB
receptors are heterodimers of two subunits, GABAB(1)
and GABAB(2) (Figure 1) (reviewed in [7,8]). In the brain,
two predominant, differentially expressed isoforms are
transcribed from the Gabbr1 gene, GABAB(1a) and
GABAB(1b), which are conserved in different species
including humans [6,9,10]. In the rat brain GABAB(1a) is
the prevalent isoform at birth whereas GABAB(1b) is more
abundant in adult brain tissue [9]. Transcription of these
isoforms is driven by different promoters and does not
involve alternative splicing. Recently, evidence shows that
GABAB(1a) and GABAB(1b) promoters are regulated differentially
by cAMP-response-element-binding protein
(CREB), activating transcription factor 4 (also known as
CREB2) and depolarization-sensitive upstream stimulatory
factor [11]. Although there is some evidence of
differential association of GABAB(1a) and GABAB(1b) with
presynaptic and postsynaptic structures, respectively, no
conclusive picture has emerged to date [7]. It seems more
likely that, depending on the brain region, GABAB(1a) and
GABAB(1b) participate in the formation of both presynaptic
and postsynaptic receptors through heterodimerization
with GABAB(2).
Additional isoforms (splice variants) of Gabbr1 have
been described [termed GABAB(1c–g)], but their physiological
significance is unclear. Partial cDNAs that correspond
to putative GABAB(2) splice variants have also been
isolated [12]. However, investigation of the Gpr51
(Gabbr2) gene structure provides no evidence that these
cDNAs correspond to additional isoforms of GABAB(2) [13].
Therefore, it seems likely that two major populations of
heteromeric GABAB receptors exist in the brain: one
containing GABAB(1a) and GABAB(2) subunits and the
other containing GABAB(1b) and GABAB(2) subunits. The
behavioural phenotypes of mice with targeted deletions
of either GABAB(1) [14,15] or GABAB(2) subunits [16] are
similar and corroborate in vitro experiments that demonstrate
that functional GABAB-receptor-mediated

Diejenigen, die meinen ersten Beitrag in diesem Thread gelesen haben, werden sich fragen, was soll dieser Verweis auf die Veröffentlichung von J.F.Cryan.
Beim Thema Angst geht es auch in diesem Forum sehr emotional zu, wie ich gehört habe auch in den Angst- SHGs. Daher als Gegensatz dieser Artikel, der sich ausschließlich rational mit dem Thema auseinandersetzt.
Der Ansatz, Angst zumindest in bestimmten Formen, als GABA-B-Rezeptordefizit zu verstehen, wird aber in der Öffentlichkeit oder der Ärzteschaft weder wahrgenommen noch akzeptiert.
Die wissenschaftliche Forschung in diesem Bereich beschränkt sich noch immer im wesentlichen auf Ratten oder Mäuse mit Isoform-Defiziten, die zum Schwimmen gezwungen werden, um zu zeigen, dass GCP 2787456 eine tolle Substanz gegen Angst ist.

Dabei wäre es doch ein Leichtes, so wie wir es mit den Umfragen gemacht haben, unsere hervorragenden Ergebnisse mit Baclofen gegen Angst und Depressionen in einem besser kontrollierten Umfeld zu wiederholen.
Ich darf erinnern: nach einer Woche Baclofen-Medikation zeigt sich bereits bei 40% der Teilnehmer an unserer Umfrage eine deutliche Verbesserung, nach ca. zwei Monaten bezeichnen sich mehr als 2/3 der Teilnehmer als frei von Angst und Depressionen.

Oder braucht es auch hier einen O. Ameisen, der das „Ende meiner Angst“ in einer mediengerechten Form darstellt und damit einen namhaften Angst- und/oder Depressionsforscher zum Googlen bringt? „Baclofen, Baclofen? Da war doch was? Könnt ich auch mal gegen Angst und Depressionen probieren."

LG invorio

...auf einer Skala von 1 bis 10...wieviel Angst hast Du noch?

@ anima
keine, aber was ist die wirkliche Frage?
LG invorio

...nur genau die gestellte...