AMG-837 is an orally bioavailable partial agonist of the GPR40 (EC50 value 13.5 nM for AMG 837 stimulated Ca2 flux in CHO cells expressing human GPR40) with a superior pharmacokinetic profile. AMG837 stimulated robust glucose-dependent insulin secretion (EC50 value 142±20 nM) in isolated rodent islets, and lowered post-prandial glucose in normal rats. Acute administration of AMG-837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG-837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. AMG-837 exhibits a potential utility for the treatment of type 2 diabetes. Amgen removed AMG-837 from Phase I clinical trials due to concerns over toxicity.

Lobelanidine is one of lobelia alkaloids that are the constituents of Lobelia inflata. Lobelia Chinensis Lour. (L. chinensis) is a plant of the Campanulaceae family that is commonly known as "xi-mi-cao", and "she-she-cao". It has been widely used as an antidote, diuretic, and hemostat in traditional Chinese medicine for decades. Lobelanidine is known for its emetic and anticancer activity.

Lobelanidine is one of lobelia alkaloids that are the constituents of Lobelia inflata. Lobelia Chinensis Lour. (L. chinensis) is a plant of the Campanulaceae family that is commonly known as "xi-mi-cao", and "she-she-cao". It has been widely used as an antidote, diuretic, and hemostat in traditional Chinese medicine for decades. Lobelanidine is known for its emetic and anticancer activity.

BMY-7378 is a multi-targeted inhibitor of α2C-adrenoceptor and α1D-adrenoceptor with pKi of 6.54 and 8.2, respectively, and acts as a mixed agonist and antagonist for 5-HT1A receptor with pKi of 8.3. BMY-7378 was at the preclinical stage of development for the treatment of anxiety disorders, but later was discontinued.

Catharanthine is a terpene indole alkaloid produced by the medicinal plant Catharanthus roseus. Catharanthine is derived from strictosidine, but the exact mechanism by which this happens is currently unknown. Catharanthine is one of the two precursors that form vinblastine, the other being vindoline.

Veratridine (VTD), an alkaloid derived from the Liliaceae plant shows anti-tumor effects. Veratridine is also an agent that opens voltage dependent Na+ channels, blocks Na+ channel activation, and induces Ca2+ influx. The compound has been observed to be an alkaloid neurotoxin used to amplify sodium permeability. Studies report that Veratridine can trigger exocytosis and induce Ca2+ oscillations. Furthermore, Veratridine has been shown to effect the mitochondrial respiratory chain complexes, induce release of noradrenaline, and increase superoxide anion production. Veratridine competes with BTX binding in a mutually exclusive manner. However, the pharmacological effects of veratridine on Na+ channels are quite different from those of BTX. First, veratridine reduces the single Na+ channel conductance drastically whereas BTX does not. Veratridine therefore is regarded as a partial agonist and BTX as a full agonist of Na+ channels. Second, under voltage clamp conditions BTX binds practically irreversibly to Na+ channels whereas veratridine readily dissociates from its binding site. Both of these drugs, however, bind preferentially to the open state of Na+ channels. The BTX resistant Na+ channels in Phyllobates frogs remain sensitive to veratridine. The ceveratrum alkaloids, including Veratridine, have a characteristic hypotensive effect not directly involving the CNS. They slow the heart and lower arterial blood pressure by reflexly stimulating medullary vasomotor centers without decreasing cardiac output (Bezold–Jarisch effect). These agents were introduced in the 1950s as antihypertensive agents; however, they were found to have a narrow therapeutic index and their use was discontinued.