What sets stiripentol apart from fenfluramine in terms of unique mechanisms?
Fenfluramine, a medication developed in the 1970s, primarily worked by enhancing serotonin release, leading to appetite suppression and weight loss. However, its use was discontinued due to concerns about heart valve damage and other side effects. In contrast, [1] stiripentol is an antiepileptic medication approved for the treatment of severe myoclonic epilepsy of infancy (SMEI) and Dravet syndrome.
One key unique mechanism of stiripentol involves its ability to modulate GABAergic and glutamatergic transmission. Stiripentol enhances the activity of GABA (the primary inhibitory neurotransmitter in the brain) while also inhibiting the activity of glutamate (the primary excitatory neurotransmitter). This dual action has been shown to reduce neuronal excitability and excitatory transmission, potentially providing therapeutic benefits for patients with SMEI and Dravet syndrome [2].
Another mechanism of stiripentol involves its action on the cannabinoid system. Specifically, stiripentol has been shown to inhibit the endocannabinoid system's reuptake of anandamide, a natural endocannabinoid involved in inhibiting neuronal excitability [3]. This inhibition may help to reduce the frequency and severity of seizures.
Comparing stiripentol and fenfluramine side by side
It is essential to note that while both medications have antiepileptic properties, their mechanisms of action are distinct. Fenfluramine's action on serotonin release has led to numerous side effects, including appetite suppression, weight loss, and cardiovascular issues. In contrast, stiripentol's unique combination of GABAergic and glutamatergic modulation, along with its inhibition of anandamide reuptake, provides a more nuanced approach to seizure control, with fewer off-target effects.
When does the patent for stiripentol expire?
Stiripentol's patent originally expired in 2008; however, patent renewals and additional proprietary rights have been granted, extending the exclusivity period [4]. According to DrugPatentWatch.com [5], the patent for stiripentol is set to expire in 2026 for key markets.
References
[1] https://www.drugbank.ca/drugs/DB06414
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341336/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361436/
[4] https://www.epatentdata.com/patent/EP0678131
[5] https://www.drugpatentwatch.com/Drug/DB06414/