Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) (GNX) is the 3beta-methylated synthetic analog of allopregnanolone; it belongs to a class of compounds referred to as neurosteroids. GNX is an allosteric modulator of GABA(A) receptors acting through binding sites which are distinct from the benzodiazepine binding site. It has activity in a broad range of animal models of epilepsy. GNX has been shown to be well tolerated in adults and children. In early phase II studies, GNX has been shown to have activity in adult patients with partial-onset seizures and epileptic children with history of infantile spasms. It is currently undergoing further development in infants with newly diagnosed infantile spasms, in women with catamenial epilepsy, and in adults with refractory partial-onset seizures. Ganaxolone is a CNS-selective GABAA modulator being developed in three different dose forms (IV, capsule, and liquid) intended to maximize therapeutic reach to adult and pediatric patients in both acute and chronic care settings.Ganaxolone is a synthetic analog of endogenous allopregnanolone, which has been shown to be an effective anticonvulsant by restoring electrical balance to the seizing brain. While allopregnanolone’s anticonvulsant and anti-anxiety activities are well documented, allopregnanolone has the potential to convert back to its metabolic precursor progesterone, which could lead to hormonal side effects. Ganaxolone has been designed with an added methyl group that prevents back conversion to an active steroid which unlocks ganaxolone’s potential for chronic use. In preclinical studies, ganaxolone exhibited potency and efficacy comparable to allopregnanolone. Both ganaxolone and allopregnanolone bind to GABAA at the synaptic and extrasynaptic binding sites. Activity with extrasynaptic GABAA receptors are of particular importance for treating patients who developed tolerance to benzodiazepines and barbiturates. Ganaxolone binds to the GABAA receptors, which opens the pore to allow chloride ions to move into the postsynaptic neuron, leading to the inhibition of neurotransmission.

Cannabidiol is the major nonpsychoactive ingredient in cannabis. Cannabidiol demonstrates a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties. Exact mechanism of action of cannabidiol is not known, but may include effects on the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 glycine receptors. GW Pharmaceuticals successfully developed the world’s first prescription medicine derived from the cannabis plant, Sativex® (buccal spray containing delta-9-tetrahydrocannabinol and cannabidiol) now approved in over 29 countries outside of the United States for the treatment of spasticity due to Multiple Sclerosis. GW Pharmaceuticals is developing Epidiolex® (a liquid formulation of pure plant-derived cannabidiol) for certain rare and severe early-onset, drug-resistant epilepsy syndromes.

Perampanel (trade name Fycompa) is an antiepileptic drug developed by Eisai Co. that acts as a selective non-competitive antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors. Although the mechanism of action through which perampanel exerts its antiepileptic effect has not been fully elucidated, this agent antagonizes the AMPA subtype of the excitatory glutamate receptor found on postsynaptic neurons in the central nervous system (CNS). This antagonistic action prevents AMPA receptor activation by glutamate and results in the inhibition of neuronal excitation, repetitive neuronal firing, and the stabilization of hyper-excited neural membranes. Glutamate, the primary excitatory neurotransmitter in the CNS, plays an important role in various neurological disorders caused by neuronal hyperexcitation. The drug is currently approved, for the control of partial-onset seizures, in those of both sexes who suffer from epilepsy and who are 12 years of age and older, by the Food and Drug Administration. Perampanel is also approved for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged 12 years and older. It is designated as a Schedule III controlled substance by the Drug Enforcement Administration. Perampanel has been studied in other clinical indications including Parkinson's disease.

Lorcaserin, currently marketed under the trade name Belviq and previously Lorqess during development, is a weight-loss drug developed by Arena Pharmaceuticals. Lorcaserin is a selective 5-HT2C receptor agonist, and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets. 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus. The activation of 5-HT2C receptors in the hypothalamus is supposed to activate proopiomelanocortin (POMC) production and consequently promote weight loss through satiety. This hypothesis is supported by clinical trials and other studies. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, and endocrine secretion, the exact mechanism of appetite regulation is not yet known. Lorcaserin has shown 100x selectivity for 5-HT2C versus the closely related 5-HT2B receptor, and 17x selectivity over the 5-HT2A receptor

Clemizole is a drug in clinical development for the treatment of hepatitis C virus (HCV) infection. Clemizole is a novel inhibitor of TRPC5 channels. Clemizole is an H1 antagonist. Clemizole, an antihistamine drug that was once widely used for treatment of allergic disease, was recently discovered to be a potent inhibitor (IC50, 24 nM) of the interaction between an HCV protein (NS4B) and HCV RNA. Although clemizole was widely used during the 1950s and 1960s, this was before contemporary regulatory requirements were established for new drug development, and there is very minimal information about its pharmacokinetics and metabolism.

Carisbamate is an experimental anticonvulsant drug that was under development by Johnson & Johnson Pharmaceutical Research and Development but never marketed. Acute and chronic nonclinical toxicological studies have not revealed any significant abnormalities other than dose-related CNS toxicity. Carisbamate displays high potency in a broad range of rodent seizure and epilepsy models at doses well below those that produce CNS toxicity. The exact mechanism of action is unknown but neuroprotective and antiseizure activity of Carisbamate likely results in part from decreased calcium accumulation through blockade of T-type Ca2+ channels. A phase II clinical trial in the treatment of partial seizures demonstrated that the compound has efficacy in the treatment of partial seizures and a good safety profile. In large multicenter phase III clinical trial for the treatment of partial seizures carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures. The most common adverse events, encountered mainly at daily doses of 1000 mg or more, were CNS-related, including headache, dizziness, somnolence, and nausea. In another phase III clinical trial, carisbamate was not more efficacious in migraine prophylaxis than placebo, but carisbamate monotherapy was well tolerated at doses up to 600 mg per day. Johnson & Johnson received provisional approval by the FDA to market carisbamate under the brand name of Comfyde. However, on August 21, 2009, Johnson & Johnson reported that the FDA had failed to give marketing approval.

Huperzine A is a plant alkaloid derived from Club moss plant, Huperzine serrata, which is a member or the Lycopodium species. Huperzine-A is in phase III clinical trial in the USA (Alzheimer disease) and is available as a dietary supplement. It selectively and reversibly inhibits acetylcholinesterase. Huperzine A is also a NMDA receptor antagonist, which protects the brain against glutamate induced damage, and it increases nerve growth factor levels. Huperzine A is used for Alzheimer's disease, memory and learning enhancement, and age-related memory impairment. It is also used for treating a muscle disease called myasthenia gravis, for increasing alertness and energy, and for protecting against agents that damage the nerves such as nerve gases. It can cause some side effects including nausea, diarrhea, vomiting, sweating, blurred vision, slurred speech, restlessness, loss of appetite, contraction and twitching of muscle fibers, cramping, increased saliva and urine, inability to control urination, high blood pressure, and slowed heart rate. Various medications used for glaucoma, Alzheimer's disease, and other conditions (Cholinergic drugs) interacts with Huperzine A.