Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) was an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects. Rimonabant is an inverse agonist for the cannabinoid receptor CB1 and was the first drug approved in that class. There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviors. It is, therefore, reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Data from clinical trials submitted to regulatory authorities showed that rimonabant caused depressive disorders or mood alterations in up to 10% of subjects and suicidal ideation in around 1%, and in Europe, it was contraindicated for people with any psychiatric disorder, including depressed or suicidal people. Additionally, nausea and upper respiratory tract infections were very common (occurring in more than 10% of people) adverse effects; common adverse effects (occurring in between 1% and 10% of people) included gastroenteritis, anxiety, irritability, insomnia and other sleep disorders, hot flushes, diarrhea, vomiting, dry or itchy skin, tendonitis, muscle cramps and spasms, fatigue, flu-like symptoms, and increased risk of falling.

Clocapramine is a chlorinated derivative of carpipramine. The hydrochloride has been given orally in the treatment of schizophrenia. Clocapramine is an antagonist of the Dopamine D2 and Serotonine (5-HT2) receptors. It has been implicated in at least one strange death, including a suicide. It augments the paroxetine in the panic disorder treatment.

Pyritinol is a semi natural analogue of water soluble vitamin B6. Pyritinol was synthetized way back in 1961 by Merck Laboratories. After years of research, it entered the market in the 1970s, where it was used for clinical applications – including treating stroke patients and those with Alzheimer’s. Since the 1990s, it has been sold as a nootropic dietary supplement in the United States and many other parts of the world. Pyritinol, unlike many other nootropics, has been approved for use as a medical treatment in countries around the world. Doctors in many European countries use Pyritinol to treat patients with chronic degenerative brain disorders – like dementia. Countries where Pyritinol is an approved treatment include Austria, Germany, France, Greece, Italy, and Portugal. France has approved the use of Pyritinol – but only as a treatment for rheumatoid arthritis. Pyritinol is not currently licensed for use in the United Kingdom, but in most other countries, it’s available online or through drug stores as an over the counter substance. Pyritinol is marketed under the brand names Encephabol, Encefabol and Cerbon 6. One of the known mechanisms of action of Pyritinol involves increasing choline uptake into your neurons and thereby increasing acetylcholine levels. Pyritinol is also a great effective precursor to dopamine, which is one of the neurotransmitter mood-boosters in the brain. Pyritinol has better conversion into the neurochemical. This drug increases dopamine, which can keep the brain from anxiety because a lower dopamine level is connected to mood disorders and depression.

The Rauwolfia alkaloid, raubasine (ajmalicine), has been found to have broad application in the treatment of circulatory diseases, especially in the relief of obstruction of normal cerebral blood flow. In combination with other Rauwolfia alkaloids it has been used to lower high blood pressure. Raubasine is an antihypertensive drug used in the treatment of high blood pressure. It has been marketed under numerous brand names including Card-Lamuran, Circolene, Cristanyl, Duxil, Duxor, Hydroxysarpon, Iskedyl, Isosarpan, Isquebral, Lamuran, Melanex, Saltucin Co, Salvalion, and Sarpan. Raubasine acts as a α1-adrenergic receptor antagonist.

Fasoracetam is a cognition enhancer that interacts with GABA(B) receptors, stimulates neuronal ACh receptors and modulates mGlu receptors. The drug is being tested in phase III/II of clinical trials for the treatment of Attention Deficit Disorder With Hyperactivity in people with genetic disorders impacting mGlu receptors and never been approved by FDA. Fasoracetam is also being marketed in the form of capsules for research purposes aimed at investigation of cognition and memory disorders.

Rilmazafone (previously known as 450191-S) is a water-soluble benzodiazepine prodrug developed in Japan. It has sedative and hypnotic effects. Rilmazafone induces impairment of motor function and has hypnotic properties. Rilmazafone has no effects on benzodiazepine receptors itself, but once inside the body is metabolised by aminopeptidase enzymes in the small intestine to form the active benzodiazepine 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo benzodiazepine-2-carboxamide. Preclinical studies have shown its excellent effects inducing and maintaining sleep with little effect on the skeletal muscle. Earlier the clinical dose for this drug as a premedicant was found to be 2-4mg.

Lenperone (AHR 2277), or 4’-fluoro-4 [4-(p-fluorobenzoyl) piperidino] butyrophenone hydrochloride, is an antipsychotic compound which has been shown in preliminary experiments to possess those features essential for neuroleptic activity. Dopamine antagonist.

Besipirdine is a potential novel first-in-class oral treatment for over active bladder currently in Phase II development, with a mechanism of action clearly different from that of antimuscarinics. It was under evaluation by Aventis up to phase III for Alzheimer’s disease, involving the administration of the compound to over 1500 patients. However, this research has been discontinued. Besipirdine antagonizes alpha-2 and alpha-1 adrenoceptors and inhibits both norepinephrine and serotonin uptake. The most common adverse events were asymptomatic postural hypotension and asymptomatic bradycardia.

Pimethixene is an antihistamine exerting sedative and antitussive properties. Pimethixene displayed high affinity to serotonin 5-HT2A and 2B, histamine H1 and muscarinic acetylcholine M2 receptors. Oral pimethixene used to calm dry cough and irritation coughs in children.

Clebopride is a dopamine antagonist drug. It is used to treat functional gastrointestinal disorder such as nausea or vomiting. Unchanged parent drug was the most abundant compound in human urine. Major metabolites included the hydroxylation at benzyl group to yield carbinolamine and its further N-dealkylation product, and the piperidine ring hydroxylation/oxidation metabolite (a lactam).