Quinolinic acid is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Elevated cerebrospinal fluid levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS. It can act as an endogenous brain excitotoxin when released by activated macrophages. Quinolinic acid is being used as a research tool to examine the role of excitotoxicity in neuronal degeneration associated with a number of neurological diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease) which involve selective neurotransmitter deficits.

PB-22, a recreational “designer drugs”, is a cannabimimetic agent, it is a full agonist of cannabinoid receptors. PB-22 has an EC50 of 5.1 nM for human CB1 receptors, and 37 nM for human CB2 receptors. PB-22 produces bradycardia and hypothermia in rats at doses of 0.3–3 mg/kg, suggesting potent cannabinoid-like activity. PB-22 was designated as a Schedule I controlled substance in the United States.

Canadine (tetrahydroberberine,THB) is an isoquinoline alkaloid (5,8,13,13a-tetrahydro-9,10-dimethoxy-6H-benzo[g]-1,3-benzodioxolo[5,6-a]quinolizine) from Corydalis tuber, it has micromolar affinity for dopamine D(2) (pK(i) = 6.08) and 5-HT(1A) (pK(i) = 5.38) receptors but moderate to no affinity for other relevant serotonin receptors (i.e., 5-HT(1B), 5-HT(1D), 5-HT(3), and 5-HT(4). Canadine enhances gastrointestinal motor function. THB, with D(2) receptor antagonist and 5-HT(1A) receptor agonist properties, has significant potential as a therapeutic for treatment of functional dyspepsia. THB is a potent inhibitor of platelet aggregation in vitro and in vivo and is a promising antithrombotic drug.

AG-3-5 (also known as icilin) was first identified as a super-cooling agent in the early 1980s and bears little resemblance to menthol structurally. Icilin is able to activate both TRPM8 and TRPA1 channel activity. Icilin alleviates pain sensation in animal models.

3-Hydroxymethyl-beta-carboline (3-HMC) is a benzodiazepine receptor antagonist both in vitro and in vivo. It antagonizes both the anticonvulsant and “anxiolytic” actions of diazepam. 3-HMC decreases sleep and reverses the hypnotic actions of flurazepam. 3-HMC is an active antagonist of the cerebrovascular and cerebral metabolic depression produced by flurazepam and can stimulate cerebral blood flow and cerebral O2 consumption at high doses when given alone. 3-HMC has the ability to specifically antagonize fentanyl anesthesia.

Grayanotoxin I is found in the leaves of plants belonging to the family Ericaceae (Leucothoe, Rhododendron, Andromeda, Kalmia). It binds to the sodium channel in its open state and upon binding the sodium channel gating is altered. A shift occurs in the activation of the sodium channel to the hyperpolarizing direction, leading to its persistent opening even at resting potentials (ranging from −70 to −100mV). In addition, the inactivation process of these modified sodium channels is suppressed. The resulting massive influx of Na+ ions will cause excitation followed by complete inexcitability of nerve cells. These lipid-soluble neurotoxins may modify sodium channels gating by causing immobilization of S6 segments during gating transitions and thereby during depolarization the channels ‘are freezed’ in the open state. In the guineapig atria, Grayanotoxin I produces a membrane depolarization, positive inotropic effects and arrhythmias.

Alpha-ergocryptine is a component of the ergotoxine complex; it is the main ergot alkaloid of Japanese & South American wid grasses. Alpha-ergocryptine is an agonist at the D2 dopamine receptor. Alpha-ergocryptine effectively decreases intraocular pressure in the alpha-chymotrypsin-induced model of ocular hypertension.

Epoxomicin was originally isolated from the culture medium of an Actinomycetes strain based on its in vivo antitumor activity against murine B16 melanoma. Epoxomicin is a selective proteasome inhibitor with anti-inflammatory activity. Despite its promising antitumor activity, epoxomicin did not draw much attention as a potential drug lead from the pharmaceutical industry, presumably because epoxomicin has seemingly poor drug-like properties, namely the presence of a peptide backbone and the labile epoxy ketone pharmacophore. Despite its drawbacks, epoxomicin’s pharmacophore was found to provide unprecedented selectivity for the proteasome. Epoxomicin also served as a scaffold for the generation of a synthetic tetrapeptide epoxyketone with improved activity.

Isatin (1H-indole-2,3-dione) is a naturally occurring heterocycle that was first synthesised by Erdmann and Laurent in 1840. Isatin possesses a wide range of biological activities. Isatin has anxiogenic, sedative, anticonvulsant activities and acts as a potent antagonist on atrial natriuretic peptide receptors in vitro. Isatin is an endogenous monoamine oxidase (MAO) inhibitor involved in stress and anxiety. Additionally, isatin inhibits alkaline phosphatase (ALP), nitric oxide (NO)-stimulated soluble guanylate cyclase, and other enzymes.

P-88-8991, (-)- is a metabolite of Iloperidone. It has functional affinity for noradrenergic, dopaminergic and serotoninergic receptors. Humans produce only one enantiomer stereospecifically following administration of Iloperidone. Preclinical studies revealed that P-88-8991, (-)- might be useful for the treatment of psychotic disorders such as schizophrenia and bipolar disorders.