Cocaine is an alkaloid ester extracted from the leaves of plants including coca. Cocaine is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine is addictive due to its effect on the reward pathway in the brain. After a short period of use, there is a high risk that dependence will occur. Its use also increases the risk of stroke, myocardial infarction, lung problems in those who smoke it, blood infections, and sudden cardiac death. Cocaine sold on the street is commonly mixed with local anesthetics, cornstarch, quinine, or sugar which can result in additional toxicity. Following repeated doses, a person may have decreased the ability to feel pleasure and be very physically tired. Cocaine acts by inhibiting the reuptake of serotonin, norepinephrine, and dopamine. This results in greater concentrations of these three neurotransmitters in the brain. It can easily cross the blood-brain barrier and may lead to the breakdown of the barrier.

Gepirone (brand name Travivo) is an investigational azapirone antidepressant and anxiolytic drug in development for the treatment of major depressive disorder but has yet to be marketed. Like other azapirones, it acts as a selective partial agonist of the 5-HT1A receptor. Gepirone has been under development in the U.S. in an extended release form (referred to as Gepirone ER). It has been rejected multiple times by the FDA during the drug approval process and Phase III studies evaluating its use in the treatment of MDD were prematurely terminated. These were the initial Phase III studies of gepirone ER in MDD, and the effective dose range had not been determined. In March 2016, the FDA reversed its decision and gave gepirone ER a positive review, clearing the way for the drug to finally gain market approval in the U.S. In addition to its antidepressant and anxiolytic properties, gepirone has been found to improve symptoms of sexual dysfunction in men and women, similarly to the marketed 5-HT1A receptor agonist flibanserin. The pro-sexual effects appear to be independent of its antidepressant and anxiolytic effects. Mechanism of action studies have demonstrated that gepirone possesses a much greater selectivity for 5-HT1A receptors over dopamine D2 receptors. Long-term studies have shown that gepirone has a differential action at presynaptic (agonist) and post-synaptic (partial agonist) 5-HT1A receptors. Treatment with gepirone ER desensitizes presynaptic 5-HT1A receptors, which decreases serotonin autoregulatory inhibition and enhances activation of postsynaptic 5-HT1A receptors. As a partial agonist gepirone ER acts as an agonist when endogenous serotonin is not present and as an antagonist when endogenous serotonin is present. Overall, gepirone ER increases serotonin production when insufficient amounts are present, and decreases serotonin production when excess amounts are present. Gepirone has been tested in Phase II clinical trial as antidepressant medication for pharmacotherapy for cocaine dependent subjects.

Vigabatrin is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin prevents the catabolism of GABA by irreversibly inhibiting the enzyme GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. However, vigabatrin is not a potent inhibitor of GABA-T with a Ki of 10 mM. Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active. Vigabatrin is sold under the trade name SABRIL, it is indicated as adjunctive therapy for adults and pediatric patients 10 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.

Tiagabine (trade name Gabitril) is an anticonvulsant medication used in the treatment of Partial Seizures. The precise mechanism by which Tiagabine exerts its antiseizure effect is unknown, although it is believed to be related to its ability to enhance the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Tiagabine binds to recognition sites associated with the GABA uptake carrier. It is thought that, by this action, Tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells. Tiagabine is approved by U.S. Food and Drug Administration (FDA) as an adjunctive treatment for partial seizures in individuals of age 12 and up. It may also be prescribed off-label by physicians to treat anxiety disorders and panic disorder as well as neuropathic pain (including fibromyalgia). For anxiety and neuropathic pain, tiagabine is used primarily to augment other treatments. Tiagabine may be used alongside selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or benzodiazepines for anxiety, or antidepressants, gabapentin, other anticonvulsants, or opioids for neuropathic pain. The most common side effect of tiagabine is dizziness. Other side effects that have been observed with a rate of statistical significance relative to placebo include asthenia, somnolence, nervousness, memory impairment, tremor, headache, diarrhea, and depression.

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is sold under the brand name Camptosar among others. CAMPTOSAR is a topoisomerase inhibitor indicated for: • First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. • Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

Selegiline, also known as L-deprenyl, is a substituted phenethylamine, a selective, irreversible inhibitor of Type B monoamine oxidase. Selegiline is available in pill form under many brand names (Eldepryl, Carbex, Atapryl) and is used to reduce symptoms in early-stage Parkinson's disease. Selegiline delays the time point when the L-DOPA (levodopa) treatment becomes necessary from about 11 months to about 18 months after diagnosis, which is beneficial despite not being definitive evidence of neuroprotection. The rationale for adding selegiline to levodopa is to decrease the required dose of levodopa and thus reduce the motor complications of levodopa therapy. Selegiline is also delivered via a transdermal patch (brand name, Emsam) and in this form, Selegiline is used as a treatment for the major depressive disorder. Selegiline (brand name Anipryl) is also used (at extremely high dosages relative to humans) in veterinary medicine to treat the symptoms of Cushing's disease and cognitive dysfunction (Canine Cognitive Dysfunction) in dogs. Side effects of the pill form include, in decreasing order of frequency, nausea, hallucinations, confusion, depression, loss of balance, insomnia, increased involuntary movements, agitation, arrhythmia, slow heart rate, delusions, hypertension, new or increased angina pectoris, and syncope. The main side effects of the patch form for depression included application site reactions, insomnia, diarrhea, and sore throat.

Prilocaine is a local anesthetic that is similar pharmacologically to lidocaine. Prilocaine binds to the intracellular surface of sodium channels which blocks the subsequent influx of sodium into the cell. Action potential propagation and never function is, therefore, prevented. This block is reversible and when the drug diffuses away from the cell, sodium channel function is restored and nerve propagation returns. Prilocaine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. Currently, Prilocaine is used most often for infiltration anesthesia in dentistry.

Neboglamine is a functional modulator of the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Neboglamine appeared to promote neuronal growth as measured by expression of Fos-like immunoreactivity, particularly in the prefrontal cortex, nucleus accumbens, and lateral septal nucleus. Neboglamine behaves as a potential antipsychotic. Neboglamine is in phase II clinical trials by Rottapharm for the treatment of schizophrenia and cocaine abuse.

Nepicastat (SYN-117) is a potent and selective inhibitor of dopamine-β-hydroxylase. This compound in Phase 2 of clinical trial for the treatment cocaine addiction and posttraumatic stress disorder.

Ritanserin (INN, USAN, BAN) is a serotonin receptor antagonist which was never marketed for clinical use but has been used in scientific research. In humans, ritanserin increases deep slow-wave sleep, improved liveliness in a variety of psychiatric disorders and facilitated participation in behaviour therapy. During clinical trials, unexpected observations indicated that ritanserin may be of value in treating obsessive-compulsive disorder, acute mania, negative symptoms of schizophrenia, drug addicts, etc. Clinical observations confirmed the efficacy of ritanserin in the chronic withdrawal phase after detoxification from ethanol. Ritanserin had been in phase III clinical trials by Janssen L.P. for the treatment of anxiety disorder and major depressive disorder. However, the clinical development of ritanserin was discontinued.