NeuroPsychiatric Symptoms from Fqs & Lariam

Some of you may be suffering from Neurospsychiatric (CNS) symptoms from Lariam or fluoroquinolones antibiotics, or other meds, including, anesthetics, both local and general anesthetic. These can manifest as very mild, moderate or very severe

Symptoms vary including, insomnia, anxiety, so called panic attacks, psychosis, hallucinations and more.

From what I read so far, CNS symptoms causes distress to many and it is important to understand and try rationalize what is happening. It is temporary, and will subside, for those who abstain from psychotropics.

My own personal view is to abstain from psychotropics no matter how severe, whilst ensuring 24 hour care if suffering from psychosis and hallucinations.

When first experiencing those symptoms, it is important to realize, that these are chemically induced. It is difficult to understand the switch from being perfectly healthy to sudden waves of overwhelming symptoms, which are often denied or attributed to anxiety and stress.

Many suffering very severe symptoms, chose to endure those symptoms opting out of psychotropics, known to cause even more damage with prolonged usage. It is also known, that worsening can occur within days of starting on some psychotropics, and certainly, long term usage, for the most part lead to tolerance level, creating a vicious cycle of worse neuropsychiatric symptoms.

Many chose to opt out of psychotropics allowing for new neural circuitry to occur, without taking psychotropics. Some recover within months, for some, it may take a few years between cycles.

There may be some lingering symptoms such as cycling insomnia, anxiety, etc... These can be controlled by observing strict diets, avoiding foods which are classified as excitory, yoga, meditation, Neurofeedback, certain vitamins and supplements, and learning how to cope with stress and symptoms.

Many will suffer not quite understanding what is happening, or believe themselves to becoming "mentally" ill, which could not be further from the truth.

The effects of these drugs are known to cause damage to neural circuitry, GABA receptors (and others), 5-HTP3 and other receptors, potassium ion channels, catecholamines, hormones, adrenals, and sometimes, heart, liver and kidneys.

Although there are several herbal remedies, either from phytomedicine, Ayurvedic medicine, and Traditional Chinese Medicine, my own view, would be to abstain, from those until there is improvement, unless, thoroughly researched under a care of a qualified practitioner. Some prefer to consult neuroscientists and psychiatrists practicing alternatives using vitamins, supplements such as amino acids, and other therapeutic protocols, such as orthomolecular, successfully.

Apart from neurotransmitters, there other factors contributing to medications causing CNS symptoms, such as ion channels. It is known that meds such as mefloquine/lariam, quinine, chloroquine, (and psychotropics) causing chaos to receptors in the brain. This article focuses on 5-HTP3 receptors.

I will post another article about potassium ion channels tomorrow. It is a fragile system, and any drug targeting neuronal circuitry will have some effect on potassium ion channels, leading to more CNS symptoms. Adding to that, drugs crossing the BBB!!

The article mentions drugs to be manufactured to target those physiological electrical signals, Mmm, as IF... AS far as I know, the best remedy is time to allow new neuronal cricuitry (neuroplasticity), which takes time, but does occur.

Ever wondered why they are not dishing out pyschotropics to strokes patients?? Beware, and research before taking any psychotropics drugs. To date, there is no scientific evidence of how psychotropics work!!


The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5-HT3 receptors
A J Thompson,1 M Lochner,1 and S C R Lummis1*
1Department of Biochemistry, University of Cambridge, Cambridge, UK
*Author for correspondence:
Received November 1, 2006; Revised January 3, 2007; Accepted January 5, 2007.

Abstract
Background and Purpose:
The antimalarial compounds quinine, chloroquine and mefloquine affect the electrophysiological properties of Cys-loop receptors and have structural similarities to 5-HT3 receptor antagonists. They may therefore act at 5-HT3 receptors.

Experimental Approach:
The effects of quinine, chloroquine and mefloquine on electrophysiological and ligand binding properties of 5-HT3A receptors expressed in HEK 293 cells and Xenopus oocytes were examined. The compounds were also docked into models of the binding site.

Key Results:
5-HT3 responses were blocked with IC 50 values of 13.4 μM, 11.8 μM and 9.36 μM for quinine, chloroquine and mefloquine. Schild plots indicated quinine and chloroquine behaved competitively with pA 2 values of 4.92 (K B=12.0 μM) and 4.97 (K B=16.4 μM). Mefloquine displayed weakly voltage-dependent, non-competitive inhibition consistent with channel block. On and off rates for quinine and chloroquine indicated a simple bimolecular reaction scheme.

Quinine, chloroquine and mefloquine displaced [3H]granisetron with K i values of 15.0, 24.2 and 35.7 μ M. Docking of quinine into a homology model of the 5-HT3 receptor binding site located the tertiary ammonium between W183 and Y234, and the quinoline ring towards the membrane, stabilised by a hydrogen bond with E129. For chloroquine, the quinoline ring was positioned between W183 and Y234 and the tertiary ammonium stabilised by interactions with F226.

Conclusions and Implications:
This study shows that quinine and chloroquine competitively inhibit 5-HT3 receptors, while mefloquine inhibits predominantly non-competitively. Both quinine and chloroquine can be docked into a receptor binding site model, consistent with their structural homology to 5-HT3 receptor antagonists.

Keywords: 5-HT3 receptor, Cys-loop receptor, binding site, ligand docking, malaria, quinine, chloroquine, mefloquine, antagonist.....

Conclusion

Cont/.....

In summary, we have used a combination of electrophysiology, ligand binding, homology modelling and simulated docking to define the mechanisms by which quinine, chloroquine and mefloquine inhibit the 5-HT3 receptor response. Our observations further extend the number of receptors known to be affected by these compounds and the growing diversity of targets may account for the broad spectrum of side effects that have been reported by patients receiving them (Luzzi and Peto, 1993; Palmer et al., 1993; Taylor and White, 2004). Inhibition of the 5-HT3-mediated current could have wide-ranging effects in the nervous system, as 5-HT3 receptors can modulate a variety of neurotransmitter responses such as those to GABA, dopamine and cholecystokinin (Thompson et al., 2006b).

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1994240

Those vids make it clear there is no scientific evidence about psychotropics efficacity, nor its mechanisms. The third vid is a good anaylysis, although not in depth.