3 replies to this topic

[kurt]

Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors.

Ivic L, Sands TT, Fishkin N, Nakanishi K, Kriegstein AR, Stromgaard K.

Department of Neurology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.

Glycine and gamma-aminobutyric acid, type A (GABA(A)) receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory synaptic transmission in the adult central nervous system. During development, the activation of these receptors leads to membrane depolarization. Ligands for the two receptors have important implications both in disease therapy and as pharmacological tools. Terpene trilactones (ginkgolides and bilobalide) are unique constituents of Ginkgo biloba extracts that have various effects on the central nervous system. We have investigated the relative potency of these compounds on glycine and GABA(A) receptors. We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA(A) receptors, with bilobalide demonstrating a more potent effect. Additionally, we provide evidence that open channels are required for glycine receptor inhibition by ginkgolides. Finally, we employ molecular modeling to elucidate the similarities and differences in the structure of the terpene trilactones to account for the pharmacological properties of these compounds and demonstrate a striking similarity between ginkgolides and picrotoxinin, a GABA(A) and recombinant glycine alpha-homomeric receptor antagonist.

Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant alpha1beta2gamma2L GABA(A) receptors.

Huang SH, Duke RK, Chebib M, Sasaki K, Wada K, Johnston GA.

Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, Faculty of Medicine, University of Sydney, NSW 2006, Sydney, Australia.

The sesquiterpene trilactone bilobalide is one of the active constituents of the 50:1 Ginkgo biloba leaf extract widely used to enhance memory and learning. Bilobalide was found to antagonise the direct action of gamma-aminobutyric acid (GABA) on recombinant alpha(1)beta(2)gamma(2L) GABA(A) receptors. The effect of bilobalide on the direct action of GABA at alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp method was evaluated and compared with the effects of the classical GABA(A) receptor competitive antagonist bicuculline and noncompetitive antagonist picrotoxinin. Bilobalide (IC(50)=4.6+/-0.5 microM) was almost as potent as bicuculline and pictrotoxinin (IC(50)=2.0+/-0.1 and 2.4+/-0.5 microM, respectively) at alpha(1)beta(2)gamma(2L) GABA(A) receptors against 40 microM GABA (GABA EC(50)). While bilobalide and picrotoxinin were clearly noncompetitive antagonists, the potency of bilobalide decreased at high GABA concentrations suggesting a component of competitive antagonism.

What does these mean? I only know I'm deficient in GABA...

[zoolander]

We find that most of the ginkgolides are selective and potent antagonists of the glycine receptor. Bilobalide, the single major component in G. biloba extracts, also reduces glycine-induced currents, although to a lesser extent. Both ginkgolides and bilobalide inhibit GABA(A) receptors, with bilobalide demonstrating a more potent effect.

Being antagonist means that they cause some sort of receptor blockade. They bind to the receptor and block receptor activation.

While bilobalide and picrotoxinin were clearly noncompetitive antagonists, the potency of bilobalide decreased at high GABA concentrations suggesting a component of competitive antagonism.

Non-competetive meaning if you increase the concentration of GABA agonists you will mostly likely decrease the receptors inhibition.

GABA receptors are probably the most common kind in the mammalian nervous system. It is estimated that close to 40% of the synapses in the human brain work with GABA and therefore have GABA receptors. GABA receptors are channel receptors. This means that when GABA binds to them, they change shape slightly to allow ions to pass through their central channel. This channel mainly allows negatively charged chloride neurons to enter the neuron, thus reducing its excitability. Because of this property of the GABA channel receptor, GABA is classified as an inhibitory neurotransmitter, as opposed to excitatory neurotransmitters, such as glutamate, which augment the nerve impulses in the neuron.

Some researchers believe that one of the purposes that GABA serves is to control the fear or anxiety experienced when neurons are overexcited.

However, this does not seem to be the case when you read further

An anxiolytic-like effect of Ginkgo biloba extract and its constituent, ginkgolide-A, in mice.

Kuribara H, Weintraub ST, Yoshihama T, Maruyama Y.

Center for Cooperative Research, Medical Division, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

The anxiolytic-like effects of Ginkgo biloba extract (GBE) and its four terpenoid components (ginkgolide-A, ginkgolide-B, ginkgolide-C, and bilobalide) were assessed using the elevated plus-maze test in mice. Administration of GBE as a single oral dose (0.5 or 1 g/kg, po) caused a state of suppressed motor activity and, thus, shortened the time spent in the open-sided arms. However, when GBE (0.063-1 g/kg, po) was administered daily for 7 days and the plus-maze test was carried out 24 h after the final administration, the time spent in the open-sided arms was prolonged, with the peak anxiolytic-like effect at 0.125 g/kg. A combination of seven-day administration of GBE (0.125 g/kg) and a single dose of diazepam (1 mg/ kg, po, 10 min before testing) enhanced the anxiolytic-like effect. Flumazenil (0.3 mg/kg, ip, 10 min before testing) blocked the effect of diazepam, but not of GBE. Daily administration of ginkgolide-A (1 or 2 mg/kg, po) resulted in an anxiolytic-like effect by the third treatment, with the maximal effect observed after the fifth administration. Neither ginkgolide-B, ginkgolide-C, nor bilobalide produced any anxiolytic-like effects. At doses higher than 0.5 g/kg, GBE not only inhibited motor activity but also suppressed active avoidance behavior, reduced caffeine-induced stimulation, and enhanced pentobarbital-induced sleep, while ginkgolide-A (up to 20 mg/kg) did not exhibit these effects. Diazepam (1 mg/kg) is known to enhance pentobarbital-induced sleep. These results suggest that GBE produces a significant anxiolytic-like effect following repeated administration and that ginkgolide-A is most likely responsible for this effect. There are also indications that although GBE exerts a sedative effect at comparatively higher doses, ginkgolide-A has a relatively weak tendency to produce benzodiazepine-like side effects.

PMID: 14575433 [PubMed - indexed for MEDLINE]

I am going to have read into this further matey.

Can anyone assist in explaining this situation??

and finally

I only know I'm deficient in GABA...

Alot of people here seem to stating that they are deficient in particular neurotransmitters. How do we know this? Please people, it is very dangerous to self diagnose! Especially when you are talking about neurotransmitter systems.

I understand that alot of people here have read "The edge effect" but the results from Bravermans survey are just guidelines. Braverman expresses this in his book.

Please be careful when self diagnosing

[kurt]

Haha...indeed I did that Bravermans survey... [lol]

[meatwad]

Please be equally careful when allowing a doctor to diagnose your body.

I believe you should tinker around! Play with your body and mind, it sure is fun.