SCH-23390 is a potent and selective antagonist of the D1A and D1B dopamine receptors having Ki of 0.2 and 0.3 nM respectively. The C11 radiolabeled version has proven to be useful as a PET imaging probe in humans for the investigation of a number of neurological conditions including Schizophrenia, Parkinson's Disease, and Huntington's Disease. It should be noted that the non-radiolabeled compound did receive preclinical interest as a potential therapeutic (annotated separately), although such efforts have been discontinued due to side-effects and a lack of therapeutic efficacy.

Sulforaphane is a naturally-occurring phytochemical belonging to the class of isothiocyanates. As the aglycone metabolite of glucosinolate glucoraphanin (sulforaphane glucosinolate), sulforaphane acts as an antioxidant and potent stimulator of endogenous detoxifying enzymes. This agent displays anticarcinogenic properties due to its ability to induce phase II detoxification enzymes, such as glutathione S-transferase and quinone reductase, thereby providing protection against certain carcinogens and toxic, reactive oxygen species. Broccoli sprouts contain large amounts of sulforaphane, which is also found in other cruciferous vegetables including cabbage and kale. Sulforaphane is under investigation for the treatment of Autism Spectrum Disorder and Schizophrenia.

PK-11195 is a selective antagonist of the Translocator Protein (TSPO). The C11 radiolabeled isotope of PK-11195 ([11C]-(R)-PK-11195) has been used effectively for diagnostic PET imaging in a number of CNS conditions where imaging of TSPO is informative (the S- enantiomer is not used). Applicable conditions including Schizophrenia, Multiple Sclerosis, and Traumatic Brain Injuries where it has been particularly useful for detection of increased microglial activation. It has also been investigated as means to monitor the role of Toll-Like Receptor-4 (TLR-4) after cerebral ischemia in mice. It should be noted that the unlabeled PK-11195 had been investigated for a number of potential therapeutic uses but did not progress beyond animal and cell models.

SB-271046 is one of the first selective 5-HT6 receptor antagonists to be discovered. SB-271046 is a potent, selective and orally active 5-HT6 receptor antagonist with a pKi value of 8.9. This compound provides a useful tool for further elucidating the physiological function of 5-HT6 receptors in vivo. SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate, as well as dopamine and noradrenaline in the frontal cortex and hippocampus of rats, and 5-HT6 antagonists have been shown to produce nootropic effects in a variety of animal studies. Suggested applications of SB-271046 included treatment of schizophrenia and other psychiatric disorders. A phase I clinical development of SB-271046 by GlaxoSmithKline (GSK) was discontinued due to a poor BBB permeability.

Lysergol {LYZ; (7-methyl- 4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinolin-9-yl)-methanol} has shown potential to enhance BA of berberine (poorly water soluble herbal anticancer agent). It is obtained from the seeds of Ipomoea muricata, I. turbinate and Calonyction muricata belonging to the family Convolvulaceae. Seeds are commonly known as ‘Kaladana’ in trade and are being used as a purgative in India and Pakistan. LYZ is an indole alkaloid present in the microfungi of Claviceps purpurea as well. It is one of the minor constituents of the ancient Mexican hallucinogenic drug Ololiuqui, which is obtained from Rivea corymbosa seeds. LYZ has been used by the 17th century midwives to induce labour and stop postpartum bleeding because of its ability to induce uterine contractions. It may also cause ergot poisoning, diarrhea, hallucinations, delirium, seizures, burning sensations, and gangrene in the limbs. However, it is not being used presently in the clinic.

Mesoridazine (brand name Serentil) is a phenothiazine antipsychotic. It was marketed in the U.S. for the treatment of schizophrenia, behavioral problems in mental deficiency and chronic brain syndrome, alcoholism and psychoneurotic symptoms, such as anxiety and tension. Due to the risk of serious cardiac events the indicated use of Serentil was limited to severely ill schizophrenic patients who fail other therapies. Based upon animal studies, mesoridazine acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. Mesoridazine shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo.

Carfenazine (brand name Proketazine) is an antipsychotic and tranquilizer of the phenothiazine group. It is used in the treatment of acute or chronic schizophrenic reactions in hospitalized patients. Proketazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis. The following is a list of possible side effects that may occur from all constituting ingredients of Proketazine: akathisia, tardive dyskinesia, extrapyramidal symptoms, allergic purpura.

LEVAMFETAMINE the levorotatory form of amphetamine. L-amphetamine, is a central nervous system (CNS) stimulant known to increase wakefulness and concentration in association with decreased appetite and fatigue. Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries. L-Amphetamine succinate was sold in Hungary between 1952 and 1955 under the brand name Cydril.

Beclamide (N-benzyl-B-chloropropionamide) is a drug that possesses anticonvulsant activity. It is no longer used. It has been used as a sedative and as an anticonvulsant. Beclamide has been used in the management of both epilepsy and behavioral disorders associated with epilepsy. It was introduced into clinical practice in 1952 under the brand names Hibicon, Lederle and later it was withdrawn. This agent was shown to be effective in grand mal but not absence seizures. Early claims emphasized its safety, and it is not entirely clear why it was withdrawn from therapy for epilepsy. Interest in the drug was rekindled in the 1990s as an adjunct in the treatment of schizophrenia.

Pregnenolone sulfate is an endogenous neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABAA receptor, a positive allosteric modulator of the NMDA receptor, and activator of transient receptor potential cation channel TRPM1 and TRPM3. In the model of schizophrenia, treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of dopamine transporter knockout mice. Promnesic properties of pregnenolone sulfate were demonstrated in rat models of spatial memory performance.