Tetraethylammonium is an experimental drug with no approved indication or marketed formulation. Tetraethylammonium blocks of apamin-sensitive and insensitive Ca2(+)-activated K+ channels. It is a weak agonist of the nicotinic receptor. Tetraethylammonium produces transient reductions in blood pressure. Tetraethylammonium hydroxide is used as a soluble source of hydroxide ions and in the synthesis of ionic organic compounds.

Trimethadione (brand name is TRIDIONE) is an oxazolidinedione compound that was developed as an antiepileptic agent for control of petit mal seizures that are refractory to treatment with other drugs. Tridione does not modify the maximal seizure pattern in patients undergoing electroconvulsive therapy and has a sedative effect that may increase to the point of ataxia when excessive doses are used. Trimethadione acts as a voltage-activated T-type Ca2+ channel blocker. Trimethadione is rapidly absorbed from the gastrointestinal tract. It is demethylated by liver microsomes to the active metabolite, dimethadione. Approximately 3% of a daily dose of tridione is recovered in the urine as the unchanged drug. The majority of trimethadione is excreted slowly by the kidney in the form of dimethadione.

Tubocurarine, a naturally occurring alkaloid, is used to treat smoking withdrawl syndrom. Tubocurarine, the chief alkaloid in tobacco products, binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of central nervous system effects are believed to be the basis of Tubocurarine's positively reinforcing properties. A stimulating effect is exerted mainly in the cortex via the locus ceruleus and a reward effect is exerted in the limbic system. At low doses the stimulant effects predominate while at high doses the reward effects predominate. Intermittent intravenous administration of Tubocurarine activates neurohormonal pathways, releasing acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH. Tubocurarine competes with acetylcholine for post-synaptic nicotinic NM receptors and blocks them.

Piperocaine (Metycaine) is a local anesthetic drug. It is an ester and primarily is a sodium channel blocker. Piperocaine can partially inhibit dopamine. It is known as a alpha-1-proteinase inhibitor. Used in the form of its hydrochloride as a local or spinal anesthetic and in dental anesthesia. Can cause toxic reactions. Piperocaine Hydrochloride is in the list of Bulk Drug Substances Nominated for Use in Compounding Under Section 503A, FDA Act. Piperocaine hydrochloride is a small, white odorless crystals or a white crystalline powder, stable in air, freely soluble in water, alcohol and chloroform.

Tricaine (MS-222, Tricaine-S), a water-soluble local anesthetic, is used commonly for sedation, immobilization, and anesthesia of poikilothermic animals and has been accepted as a common anesthetic for use in the cold-blooded animals. It has long been recognized as a valuable tool for the proper handling of these animals during manual spawning (fish stripping), weighing, measuring, marking, surgical operations, transport, photography, and research. Tricaine was developed by Merck as a sulfonated analog of benzocaine with high solubility in water. The main advantage of Tricaine is the short duration of action and rapid metabolism. There are many reports describing the use of Tricaine for anesthetizing poikilothermic animals because it is a safe agent for immersion anesthesia even though the other anesthetics such as ether, ethanol, thiopental, halothane, isoflurane, barbiturates also could be used. Amphibians could be anesthetized easily by immersion methods with Tricaine because the amphibian skin is extremely permeable and water is absorbed through the skin rather than ingested. Tricaine has been administered as an injectable agent also.

Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine. Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.

Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. Nuciferine was studied as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels. In addition, was suggested, that nuciferine had atypical antipsychotic-like actions. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In addition, was shown, that that nuciferine had a therapeutic effect on respiratory diseases associated with the aberrant contraction of airway smooth muscles and/or bronchospasm through the blockade of voltage-dependent L-type Ca2+ channels and/or nonselective cation channels.

Rhynchophylline is an alkaloid found in certain Uncaria species (Rubiaceae), notably Uncaria rhynchophylla, Uncaria tomentosa and Gambirplant (Gouteng). The total alkaloid content in Uncaria rhynchophyl-lina is about 0.2 %, in which rhynchophylline (Rhy) is 28 %-50 %, isorhynchophylline is 15 %. The pharmacological effects of Rhynchophylline and Isorhynchophylline were extensively studied, especially in the cardiovascular system. The hypotensive effect of Rhynchophylline was also observed in 1978. The peculiarity of Rhynchophylline was that renal blood flow was not significantly interfered upon lowering of blood pressure. Although the effect of Rhynchophylline on the renin secretion remained unclear, the consequence of Rhynchophylline on the renal blood flow ought to be considered as an advantage. The cardiovascular effects of Rhy were supposed due to calcium channel block. In an experiment with the guinea pig, Rhy inhibited the left atrium post-rest potential enhancement and staircase phenomenon. The post-rest potential enhancement induced by Auxo-frequency stimulation is the characteristic of Ca(‘2+) influx increase, and the calcium antagonists, such as verapamil, can reverse the staircase phenomenon. In isolated strips of rabbit aorta, Rhynchophylline inhibited 45Ca(‘2+) influx induced by K(‘+). Effects of Rhynchophylline on the 45Ca2+ influx and efflux induced by noradrenaline were small. The vasodilative effect of Rhynchophylline was mainly due to the dysfunction of Ca(‘2+) transport, including the influx of extracellular calcium and release of intracellular calcium by blocking the voltage-dependent calcium channel and the receptor-regulation calcium channel. Brachycardia and cardiac contractility repression induced by Rhynchophylline were observed. Rhynchophylline inhibited rabbit platelet aggregation induced by arachidonic acid (AA), collagen, and ADP, and reduced the thromboxane B2 (TXB2) generation in platelet-rich plasma (PRP) induced by collagen but failed to reduce TXB2 generation that induced by AA. Rhynchophylline suppressed malondialdehyde (MDA) formation in platelet suspension stimulated by thrombin, inhibited the platelet factor 4 (PF4) release. It did not alter intraplatelet cAMP concentration. Rhynchophylline 10-20 mg/kg iv showed a significant inhibition of venous thrombosis and cerebral thrombosis in rats. Rhynchophylline can relieve contraction of the respiratory tract smooth muscle and uterus smooth muscle induced by the agonist, in which a mechanism of calcium channel blocking was also proposed. In a cultured brain slice of rats, Rhynchophylline increased the 5-HT content in the hypothalamus and cortex but reduced the dopamine (DA) concentrations in the cortex, amygdala, and spinal cord. Rhynchophylline promoted the release of endogenous DA from hypothalamus, cortex, amygdala, and spinal cord. The release of 5-HT was increased in cortex and amygdala and was decreased in hypothalamus slice. However, Rhynchophylline inhibited the release of both 5-HT and DA evoked by high potassium. Rhynchophylline can protect neurons from damage induced by dopamine, which behaves as a free radical at higher concentration.

Afoxolaner (brand name NexGard) is a member of an isoxazoline class of compounds, which is used to kill adult fleas and is indicated for the treatment and prevention of flea infestations, and the treatment and control of Black-legged tick, American Dog tick, Lone Star tick, and Brown dog tick infestations in dogs and puppies. Afoxolaner is a member of the isoxazoline family, shown to bind at a binding site to inhibit insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking pre- and post-synaptic transfer of chloride ions across cell membranes. Afoxolaner blocks native and expressed insect GABA-gated chloride channels with nanomolar potency. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines.

Alfaxalone is a rapidly acting hydrophobic synthetic neurosteroid. It is indicated for the induction and maintenance of anesthesia and for induction of anesthesia followed by maintenance with an inhalant anesthetic, in cats and dogs. Alfaxalone induces anaesthesia through activity at the gamma amino butyric acid sub-type A receptor (GABAA) present on cells in the Central Nervous System (CNS). Alfaxalone enhances the effects of GABA at the GABAA receptors resulting in opening of channels into the cells and an influx of chloride ions. This causes hyperpolarisation of the cells and inhibition of neural impulse transmission. Alfaxalone can be safely combined with premedicants (xylazine, (dex)medetomidine, acepromazine, midazolam), opioids (morphine, methadone, hydromorphone, butorphanol, nalbuphine, buprenorphine, fentanyl), and NSAIDs. Alfaxalone’s adverse reactions are: hypotension, tachycardia, apnea, hypertension, bradypnea and others.