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Has anybody who has had success with Abilify tried Zonegran?

I was exploring possible treatments for myoclonic jerks, which a lot of us from, and I came across Zonisamide or Zonegran. It has an interesting affect on microglia and dopamine.

Zonisamide (Zonegran) has several effects on microglial activation and dopamine in Parkinson's disease:

1. Microglial effects:
- Zonisamide reduces microglial activation in the striatum and other brain regions, as evidenced by decreased Iba1 immunofluorescence staining and F4/80 mRNA expression[2].
- It suppresses neuroinflammation by attenuating the activation of microglia, as shown in PET imaging studies using [11C]DPA713 binding[5].
- Zonisamide ameliorates microglial mitochondrial dysfunction in Parkinson's disease models[4].

2. Dopamine-related effects:
- Zonisamide protects dopaminergic neurons from degeneration, particularly in the nigrostriatal pathway[2].
- It suppresses the decline of dopamine transporter binding in the nucleus accumbens, suggesting a protective effect on presynaptic dopaminergic terminals[5].
- Zonisamide may increase dopamine synthesis and turnover in Parkinson's disease patients[5].

3. Neuroprotective mechanisms:
- The drug inhibits microglial NADPH oxidase activity, reducing the release of reactive oxygen species and inflammatory cytokines[4].
- Zonisamide partially reverses the expression of mitochondrial proteins like Timm23 in activated microglia[4].

These effects indicate that zonisamide has neuroprotective properties in Parkinson's disease by modulating microglial activation and supporting dopaminergic neuron health. The drug's ability to reduce neuroinflammation and protect dopamine neurons may contribute to its therapeutic benefits in treating Parkinson's disease.
From AI perplexity

Nigrostriatal pathway cfs​

The nigrostriatal pathway is a critical dopamine pathway in the brain that plays a crucial role in movement and motor control. While there is no direct evidence linking the nigrostriatal pathway to Chronic Fatigue Syndrome (CFS), some research suggests that alterations in dopamine signaling may contribute to the pathophysiology of CFS.
Dopamine and CFS
  • Dopamine dysregulation: Some studies have reported altered dopamine levels and receptor binding in individuals with CFS, suggesting potential dysregulation of the nigrostriatal pathway.
  • Fatigue and dopamine: Dopamine is involved in regulating motivation, reward, and movement. Altered dopamine signaling may contribute to the experience of fatigue in CFS patients.
  • Cognitive impairment: Dopamine is also involved in cognitive processes, and alterations in dopamine signaling may contribute to cognitive impairment observed in some CFS patients.
Potential Implications for CFS Treatment
  • Dopamine agonists: Targeting the nigrostriatal pathway with dopamine agonists may potentially alleviate symptoms of CFS, such as fatigue and cognitive impairment.
  • Neurotransmitter modulation: Modulating dopamine and other neurotransmitters may help restore normal brain function and alleviate symptoms in CFS patients.
While the relationship between the nigrostriatal pathway and CFS is still unclear, further research is needed to fully understand the potential implications for treatment.
AI opinion on Zonisamide and dopamine.

Zonegran (zonisamide) does appear to regulate dopamine in several ways:

1. It increases intracellular dopamine concentration when administered at doses of 25-50 mg/kg daily for 3 weeks[3][4].

2. Zonisamide enhances dopamine synthesis by increasing tyrosine hydroxylase activity in the striatum[1][4].

3. It increases dopamine turnover, helping surviving dopaminergic neurons recover dopamine production[3][4].

4. Zonisamide increases extracellular dopamine concentration, possibly by suppressing dopamine reuptake[4].

5. It may increase the release of dopamine, though some recent studies have questioned this mechanism[4].

6. Zonisamide appears to protect dopamine-producing cells in animal models of Parkinson's disease[3][4].

7. It delays the reduction of striatal presynaptic dopamine transporter levels, potentially slowing early-stage Parkinson's disease progression[3][4].

8. Zonisamide mitigates the loss of dopamine terminals in certain brain regions like the nucleus accumbens[5].

While the exact mechanisms are still being studied, the evidence indicates that zonisamide has multiple effects on dopamine regulation, synthesis, and neuroprotection of dopaminergic neurons. These effects likely contribute to its therapeutic benefits in Parkinson's disease.
It’s the second point of the post above that interests me;

2. It has a biphasic, concentration-dependent effect on dopamine exocytosis (release). At lower doses equivalent to antiepileptic doses, it increases dopamine release, while higher doses inhibit release[1].

As with Abilify, Zonegran is biphasic and increases intracellular dopamine.
When I asked AI about dosage for increasing dopamine in the brain, it came up with this;

Based on the search results, the lower end of therapeutic doses of Zonegran (zonisamide) for increasing dopamine in brain cells appears to be around 20-25 mg/day. Here are the key points:

1. In animal studies, doses of 20 mg/kg and 50 mg/kg have been shown to increase both intracellular and extracellular dopamine levels in the rat striatum and hippocampus[2].

2. For Parkinson's disease treatment in humans, therapeutic doses are typically 25-100 mg/day, which are considerably lower than those used for epilepsy treatment (200-400 mg/day)[2].

3. A clinical study by Murata et al. found that doses of 25 mg and 50 mg per day were effective in improving motor symptoms in Parkinson's disease patients, with 25 mg showing significant improvements compared to placebo[1][4].

4. The lower doses (25-50 mg) of zonisamide tend to increase dopamine levels, while higher, supratherapeutic doses may actually decrease intracellular dopamine[2][4].

5. Acute administration of 20 and 50 mg/kg doses increased striatal extracellular DOPA levels and intracellular striatal and hippocampal DOPA in animal studies[5].

Therefore, the lower end of the therapeutic dose range for increasing dopamine in brain cells appears to be around 20-25 mg per day, based on both animal studies and human clinical trials.
I’ve just ordered Zonegran from AllDayChemist. I will experiment taking a combo of low dose Zonegran and low dose Abilify. I’m trying this because I can’t find a record of any ME/CFS sufferers trialling Zonegran.

I will keep this thread posted.
Zonisamide (Zonegran) has been shown to have effects on dopamine D2 receptors, which may contribute to its therapeutic benefits:

1. Zonisamide directly activates dopamine D2 receptors[3]. This activation of D2 receptors could play a role in its mechanisms of action.

2. In the context of weight loss, dopamine D2-receptor agonists are known to inhibit feeding. Obese individuals have been found to have reduced density of striatal D2 receptors[4]. Zonisamide's effects on D2 receptors may therefore contribute to its potential as a weight loss medication.

3. Zonisamide enhances dopamine synthesis, leading to increased levels of intracellular dopamine and its metabolites[4]. This increase in dopamine availability could further stimulate D2 receptors.

4. At therapeutic doses, zonisamide has been shown to enhance dopamine synthesis and turnover[4]. This effect on the dopamine system, including D2 receptors, may be relevant to its efficacy in treating conditions like Parkinson's disease.

5. Some research suggests that zonisamide may stimulate D2 receptors directly, in addition to its effects on dopamine synthesis and availability[4].

These effects on D2 receptors and the dopamine system more broadly may contribute to zonisamide's therapeutic effects in epilepsy, Parkinson's disease, and potentially other conditions like obesity.