Idiopathic generalized epilepsy (IGE) is a major health concern, constituting up to one third of epilepsies (1). They are determined by genetics and affects people of all sexes and races. Many IGEs are lifelong, and have an onset during childhood or adolescence (1). One drug that is used to treat IGEs is the barbiturate, phenobarbital (2). This medication is one of the oldest available antiepileptics, and is low cost and effective (2). However, there are some serious side effects of the drug which include somnolence, neuralgic pain, hyperactivity, hypotension, respiratory depression and impairment of fine motor skills (3). Barbiturates affect the GABA receptor, specifically the GABAA receptor and are transmitter-gated ion channels (4).…show more content… Barbiturates also do this via their effect on glutamate receptors by inhibiting the AMPA subtype of glutamate receptor (7,8).
The increased inhibition of barbiturates leads to depression of the body. It includes depression of smooth muscles (such as lowering of heart rate, respiration, and blood pressure), depression of skeletal muscles, diminished brain function (such as impaired judgement), sedation, and altered emotional responses (9). Some other common side effects, particularly of phenobarbital, includes dizziness, drowsiness, problems with memory/concentration, nausea, and vomiting. (9).
Phenobarbital would be my drug of choice within the barbiturate class of drugs. I would choose to target these class of drugs for epilepsy due to their potency and yet the severity of side effects. As one of the oldest epileptic drugs, there is room for improvement with phenobarbital, particularly with the side effects mentioned. Also of note, there was a study that looked at possibly combining a NKCC1 inhibitor, such as bumetanide, with phenobarbital to increase the action of the barbiturate (4) or the combination of phenobarbital and phenytonin (10). I would use these ideas as a launching point for my research.
If the medicinal chemists could synthesize the drugs that I would use for future experimentation, and assuming there is no limit to my funding, I would conduct experiments that would determine the pharmacokinetics, the pharmacodynamics, the