Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. Once ingested, psilocybin is rapidly metabolized to the psilocin, which then acts on serotonin receptors in the brain. Psilocybin was identified as the active hallucinogenic compound in magic mushrooms in 1959, but humans have used assorted psilocybin mushrooms in religious ceremonies since prehistoric times. In the 1960's psilocybin was marketed for use as a treatment for various psychoses, however, it was withdrawn from the market when the regulatory environment changed. Recently there has been as renewed interest in studying the medicinal uses of psilocybin for treatment of anxiety, depression, migraine headaches, addictions, and other neuropsychiatric conditions.

Conessine is a plant steroid alkaloid that acts as a potent and specific antagonist of histamine H3 receptors. Conessine displayed high affinity at both rat and human H3 receptors (pKi = 7.61 and 8.27) and generally high selectivity against other sites, including histamine receptors H1, H2, and H4. Conessine was found to efficiently penetrate the CNS and reach very high brain concentrations. Although the very slow CNS clearance and strong binding to adrenergic receptors discouraged focus on conessine itself for further development, its potency and novel steroid-based skeleton motivated further chemical investigation. Modification based on introducing diversity at the 3-nitrogen position generated a new series of H3 antagonists with higher in vitro potency, improved target selectivity, and more favorable drug-like properties. Conessine also has high affinity for the adrenergic receptors. Conessine has being shown to possess anti-malarial activity. In India conessine finds therapeutic use for treatment of dysentery and helminthic disorders.

Vinrosidine (leurosidine) is a leurosine-like alkaloid originally isolated from Vinca rosea Linn. Vinrosidine exerts antitumor activity in animal models.

Vinepidine, a derivative of vincristine participated in clinical trials as an antineoplastic agent. As a result, the extreme neuromuscular toxicity was observed, that is why this study was discontinued.

Eprodisate (1,3-propanedisulfonate) is a negatively charged, sulfonated molecule of low molecular weight that has structural similarities to heparin sulfate; it is a glycosaminoglycan mimetic that binds to the glycosaminoglycan (GAG) binding site on serum A amyloid (AA) to prevent its interaction with glycosaminoglycan and arrest amyloidosis, or inhibit amyloid deposition. In nonclinical toxicity studies in two animal species (i.e., rat and dog), eprodisate was administered orally at doses of up to 2000 mg/kg/day for 39 weeks: eprodisate showed low toxicity potential at doses several fold higher than the anticipated clinical dose, was well tolerated upon chronic exposure and was found to be nonmutagenic and nonclastogenic. Furthermore, a series of safety pharmacology studies showed that eprodisate does not have any clinically significant effect on major organ function.

Xorphanol (also known as TR5379M) is a full κ-opioid receptor agonist and is a partial agonist at μ opioid receptor. Clinically, xorphanol was studied as an orally active analgesic that provided effective pain relief but showed low physical dependence liability. Further development of this drug was discontinued.

Squalamine is a steroid-polyamine conjugate compound with broad-spectrum antimicrobial activity and anti-angiogenic activity. Squalamine selectively inhibits new blood vessel formation; this activity is thought to be mediated through inhibition of the sodium-hydrogen antiporter sodium-proton exchangers (specifically the NHE3 isoform) causing inhibition of hydrogen ion efflux from endothelial cells, with subsequent reduction of cellular proliferation. Studies in tumor-bearing mice have shown that squalamine inhibits angiogenesis and tumor growth in xenograft models of lung, breast, ovarian, and prostate cancer and in brain and breast allograft tumor models in rats. Squalamine also has been shown to prevent lung metastases in the murine Lewis lung carcinoma model, both as a single agent and in combination with various other chemotherapeutics. Squalamine does not appear to have substantial direct effects on primary tumor growth in animal models when administered as a single agent. However, enhanced antitumor responses are observed when squalamine is administered in combination with cytotoxic chemotherapeutic agents when compared with cytotoxic agents used alone. Squalamine was studied as a potential cancer drug and as a potential treatment for wet macular degeneration but as of 2018 had not succeeded in Phase III trials for any use.

Proxorphan is a N-substituted 6-oxamorphinane patented by American pharmaceutical company Bristol-Myers Co. as opioid analgesic and antitussive drug. Proxorphan acts as a κ-opioid receptor partial agonist and to a lesser extent as a μ-opioid receptor partial agonist.

Vinleurosine is a vinca alkaloid found in species of Catharanthus. This compound was studied as an anticancer agent and participated in clinical trials. However, the drug was more toxic and unpredictable in effect in comparison with vinblastine. Its further development was discontinued.

Coniine is a neurotoxic piperidine alkaloid found in poison hemlock (Conium maculatum L.). Coniine which is considered to be racemic mixture first described by Gieseke in 1827; von Hoffman confirmed the structure in 1881; Ladenburg perfermed synthesis in 1886. Coniine enantiomers are nicotinic acetylcholine receptor (nAChR) agonists. The relative potencies of these enantiomers on TE-671 cells expressing human fetal nicotinic neuromuscular receptors had the rank order of (-)-coniine > (+/-)-coniine > (+)-coniine. The rank order potency in SH-SY5Y cells which predominately express autonomic nAChRs was: (-)-coniine>(+)-coniine> (+/-)-coniine.