MERSALYL (Mersal) is an organomercury compound, mercurial diuretics that superseded by safer diuretics such as thiazides, and is hardly used anymore. Due to the idiosyncratic nature of mercury toxicity, the risk of severe disease and sudden death are unpredictable and frequently show no warning signs. Mercurial diuretics cause diuresis by reducing the reabsorption sodium in the ascending loop of Henle, thus causing more water being delivered to the distal convoluted tubule. Unfortunately, earlier physicians misconstrued hallmark symptoms of mercury poisoning such as excessive salivation as signs of mercury's efficacy, including up until the early 1960s when the use of mercurial diuretics was halted in medicine.

Cevadine, veratridine, and related lipophilic ceveratrum alkaloids cause activation of the voltage-sensitive Na+ channels of nerve, heart, and skeletal muscle cell membranes similar to pyrethrins. Both veratridine and cevadine alter the ion selectivity of Na+ channels and cause persistent activation. The receptor for these alkaloids has not been isolated, but experiments indicate it is distinct from that of pyrethrin. Structurally, veratridine and cevadine differ only in their acyl group. Cevadine has been used as an insecticide, acting as a paralytic agent with higher toxicity to insects than to mammals. It has been used to study Na+ channel blockers such as vincamine and vincanol by inducing Na+ channels in the presence and absence of the drugs being tested.

Succinic acid is a dicarboxylic acid, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA), an energy-yielding process shared by all organisms. Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh's disease, and Mela's disease and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury. Succinic acid is a precursor to some polyesters and a component of some alkyd resins. Succinic acid also serves as the bases of certain biodegradable polymers, which are of interest in tissue engineering applications. As a food additive and dietary supplement, succinic acid is generally recognized as safe by the U.S. Food and Drug Administration. Succinic acid is used primarily as an acidity regulator in the food and beverage industry. It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste.[11] As an excipient in pharmaceutical products, it is also used to control acidity or as a counter ion. Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate.

Aluminium silicate is a compound made from aluminum, oxygen and silicate that can take the form of a mineral as well as combine with water to make a clay. Aluminum silicate comes in three mineral forms: andalusite, kyanite and sillimanite, all of which have the chemical formula Al2SiO5 but have distinct crystal structures. When magnesium aluminum silicate is hydrated it becomes a clay known as kaolin, which is used for treating ailments such as diarrhea and to combat diaper rash as well as rashes from poison oak and poison ivy. When combined with magnesium and hydrated, the result is a clay mixture that sees common use in antacids as well as a thickener for cosmetics and other beauty products. It also appears as an inactive ingredient for deodorants. The kyanite form of aluminium silicate is used to create mullite for industrial use, and this compound is used by the ceramics industry as a refractory, as well as to manufacture electrical insulating materials and heating elements. Aluminium silicate (aluminum oxide silicate), under the brand name Adsorbin among others, is used as antidiarrheal agent and intestinal adsorbent. Kaolin (hydrated aluminum silicate) has traditionally been used internally to control diarrhea. Kaolin has also been used topically as an emollient and drying agent. Specifically, it has been used to dry oozing and weeping poison ivy, poison oak, and poison sumac rashes. It has also been used as a protectant for the temporary relief of anorectal itching and diaper rash.

Theobromine is the primary alkaloid present in the cocoa and chocolate. Theobromine is found in the shells and beans of the cacao plant and it is extracted from the husks of the bean and used for the synthesis of caffeine. Theobromine is an adenosine A1 and A2a receptor antagonist. Thesodate is used as a vasodilator, a diuretic, and heart stimulant. And similar to caffeine, it may be useful in management of fatigue and orthostatic hypotension. The symptomatic adverse reactions produced by theobromine are more or less tolerable and if they become severe, they can be treated symptomatically, these include anxiety, restlessness, tremors, sleeplessness, nausea and vomiting, loss of appetite. Theobromine is currently not in use as a medicinal drug.

Amosulalol is a beta- and alpha-1 adrenoceptor-blocking agent developed for the treatment of hypertension. Amosulalol does not cross blood brain barrier and does not have adverse affect on CNS system.The drug is marketed under the name Lowgan in Japan and Korea.

Isorhynchophylline is a plant alkaloid isolated from Uncaria species with therapeutic potential for cardiovascular and central nervous system diseases. The antihypertensive effect of isorhynchophylline was firstly observed in 1989, which was strongly linked to the traditional use of Uncaria species (Gouteng in Chinese). Isorhynchophylline and rhynchophylline were the main hypotensive constituents in Uncaria rhynchophylla. In rat isolated mesenteric arteries and tail artery, isorhynchophylline inhibited the increased infusion pressure induced by high K+ and norepinephrine in a concentration-dependent manner. The potency of isorhynchophylline and rhynchophylline was similar in mesenteric arteries, but in the tail artery, the effect of isorhynchophylline on high K+ induced infusion pressure increase was stronger than that of rhynchophylline, and there was a similar trend in the contractile response induced by norepinephrine. Isorhynchophylline also inhibited the hypertensive effect of angiotensin II. The results indicate that in small blood vessels of rat, isorhynchophylline can directly inhibit the contractile responses induced by several agonists. In vivo, ouabain and CaCl2 were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-clamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. Isorhynchophylline, infusion 0–16 mg/kg at a constant rate, dose-dependently decreased heart rate, prolonged sinus node recovery time, and PR, AH, HV intervals. Isorhynchophylline significantly inhibited the heart rate and atrioventricular conduction. These inhibitory effects of isorhynchophylline were partially antagonized by isoprenaline, but not by atropine. Isorhynchophylline inhibited the automaticity and contractile force of isolated guinea pig atrium in a concentration-dependent manner. Isorhynchophylline significantly depressed adrenaline-induced automaticity, and prolonged functional refractory period and decreased excitability. Furthermore, 10 μmol/L of isorhynchophylline reduced the effect of ouabain on the contractile force in the left atrium and significantly inhibited the response to paired stimulation. In anesthetized dogs, isorhynchophylline markedly reduced the tension-time index which indicated myocardial oxygen consumption. The result indicates that the decrease of myocardial oxygen consumption by isorhynchophylline would protect the heart against ischemia induced by hypertension. Isorhynchophylline showed a mild central depressive effect in mice. Isorhynchophylline significantly decreased locomotor activity after oral administration to mice. The depression of locomotor activity upon administration of the alkaloid appears to be due to mediating of the central dopaminergic system. Isorhynchophylline dose-dependently inhibited 5-hydroxytryptamine (5-HT)2A receptor-mediated head-twitch but not 5-HT1A receptor-mediated head-weaving responses evoked by 5-methoxy-N, N-dimethyltryptamine. Isorhynchophylline attenuated the in vitro ischemia-induced neuronal damage in a dose-dependent manner. Isorhynchophylline protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in β- amyloid(25–35)-induced neurotoxicity in rat pheochromocytoma cells. In unthoracotomized dogs, isorhynchophylline (5 mg/kg, iv) reduced the mean arterial pressure but did not affect renal blood flow. Isorhynchophylline did not block nictitating membrane contraction induced by stimulating collum sympathetic nerve and did not decrease blood pressure after injected in the cerebral ventricle.

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.

Cinnamic acid is a polyphenol found in cinnamon oil and used in commercial flavorings. Recent studies have shown the pharmacological properties of cinnamic acid and its derivatives, including hepatoprotective, anti-oxidant, and anti-diabetic activities. In preclinical studies cinnamic acid demonstrated to be a promising candidate for the treatment ob obesity and diabetes. The mechanism of action of cinnamic acid in obesity is explained by its ability to inhibit lipases and ACE (angiotensin-converting enzyme). However, there are several hypotesis regarding the effect of cinnamic acid in diabetes: cinnamic acid enhances glucose-induced insulin secretion, prevents palmitic acid-induced lipotoxicity, inhibits palmitic acid-induced alteration of lipogenic gene and protein expression (AMPK, SREBP-1c, FAS, ACC), inhibits DPP IV, exhibits an additive effect on the uptake of glucose, stimulates adiponectin secretion, etc.

Stevioside is an ent-kaurene type diterpenoid glycoside isolated from leaves of Stevia rebaudiana (Bertoni) Bertoni, a perennial herb of the asteraceae (compositae) family. Stevioside and related compounds are responsible for the sweet taste of Stevia leaves. Stevioside is an intense sweetener and the extract of its source (S. rebaudiana) finds extensive use in countries like Japan, China, Russia, Korea, Paraguay, Argentina, Indonesia, Malaysia, Australia, New Zealand, South America, and others, to sweeten local teas, medicines, food, and beverages. Stevia leaves are also in use for their medicinal benefits in hypertension, obesity, topical dressing for wounds, and other skin disorders. Oral stevioside is not taken up by the human body (or the uptake is extremely low) and none of the digestive enzymes from the gastro-intestinal tract of different animals and human body are able to degrade stevioside into steviol. A number of studies have suggested that, beside sweetness, stevioside along with related compounds, which include rebaudioside A, steviol and isosteviol may also offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions.