Moxidectin is a semi-synthetic methoxime derivative of LL F-2924α, commonly referred as F-alpha or nemadectin F-alpha is a product of fermentation of Streptomyces cyaneogriseus subsp. noncyanogenus, a bacterial organism isolated in 1983 from a sample of sand from Victoria, Australia. Moxidectin is a potent, broad-spectrum endectocide with activity against a wide range of nematodes, insects and acari. The compound acts by binding to ligand-gated chloride channels, more specifically the subtypes that are gamma-aminobutyric (GABA) mediated and glutamate-gated. The consequence of Moxidectin binding and activation is an increased permeability, leading to an influx of chloride ions and flaccid paralysis of the parasite leading to death. The macrocyclic lactones probably act by binding to and opening glutamate-gated chloride channels found only in neurons and myocytes of invertebrates. Because moxidectin is very lipophilic, it becomes highly concentrated in the serum. When the concentration of moxidectin in the serum is high, moxidectin is able to cross the blood-brain barrier. Once it is in the central nervous system, a macrocyclic lactone stimulates the synaptic secretion of the inhibitory neurotransmitter, GABA. By binding at the receptor site, GABA causes influx of chloride ions into neurons, causing the neurons to become hyperpolarised, which in turn, causes diminution in neuronal activity, resulting in sedation and relaxation of the skeletal muscles. Signs displayed by foals with moxidectin toxicity included dyspnoea, depression, ataxia, weakness, coma and seizures. In a Phase 3 study compared the efficacy, safety and tolerability of moxidectin and ivermectin in subjects infected with Onchocerca volvulus, which is the parasite that causes river blindness.

Diazoxide is a drug which was approved by FDA for the treatment of secondary hyperinsulinemia. The drug exerts its action by binding to SUR1 subunit of ATP-sensitive potassium channel that leads to the channel opening.

BMS-191011, an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. BMS-191011 demonstrated efficacy as an opener of the cloned large-conductance Ca2+-activated potassium (maxi-K) channel in in vivo stroke models

Flindokalner (BMS 204352; MaxiPost™) is a neuroprotective agent with potential in the treatment of stroke developed by Bristol-Myers Squibb. Flindokalner is a potent and effective opener of two important subtypes of neuronal potassium channels, the calcium-activated, big-conductance potassium channels (K(Ca) channels) and voltage-dependent, non-inactivating potassium channels known as KCNQ channels. Flindokalner significantly reduced cortical infarct volume in a animal models of stroke. Flindokalner failed to show superior efficacy in acute stroke patients compared to placebo in a Phase III study.

Cromakalim is an ATP-sensitive potassium (KATP) channel opener, which was studied for the treatment of gastric ulcer, hypertension and preventing a cardiomyopathy. But the development of this drug was discontinued due to heart lesions found in monkey chronic toxicity studies.

Isopimaric acid is a widely available tricyclic diterpenoid well represented in the resin of conifers of the genera Pinus, Larix, and Picea. It exhibits interesting biological and pharmaceutical properties such as antimicrobial, antiviral, antiallergenic, and anti‐inflammatory activities. It acts as a large conductance Ca2+activated K+ channel (BK channel) opener. BK channel openers have emerged as potentially useful agents in the therapy of various diseases associated with both the central nervous system and smooth muscle system.

Pimaric acid is a carboxylic acid from the resin acid group. It is a BK-channel opener and inhibits TNF-alpha induced signaling by downregulating NF-kB and AP-1.