MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine. It is of interest as a precursor to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study disease models in various animals.
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifically, a neurotoxin or neurotoxicant– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to nervous tissue. This can eventually disrupt or even kill neurons, which are cells that transmit and process signals in the brain and other parts of the nervous system. Neurotoxicity can result from organ transplants, radiation treatment, certain drug therapies, recreational drug use, exposure to heavy metals, bites from certain species of venomous snakes, pesticides, certain industrial cleaning solvents, fuels and certain naturally occurring substances. Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness, loss of memory, vision, and/or intellect, uncontrollable obsessive and/or compulsive behaviors, delusions, headache, cognitive and behavioral problems and sexual dysfunction. Chronic mold exposure in homes can lead to neurotoxicity which may not appear for months to years of exposure. All symptoms listed above are consistent with mold mycotoxin accumulation.
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Otto Eisleb, its analgesic properties were first recognized by Otto Schaumann while working for IG Farben, in Germany. Pethidine is the prototype of a large family of analgesics including the pethidine 4-phenylpiperidines, the prodines, bemidones and others more distant, including diphenoxylate and analogues.
J. William Langston is the founder and chief scientific officer, movement disorder specialist, and chief executive officer of the Parkinson's Institute and Clinical Center in Sunnyvale, California, the founding member of the Scientific Advisory Board for the Michael J. Fox Foundation and the Co-Editor-in-Chief of the Journal of Parkinson's Disease. He is a graduate of the University of Missouri School of Medicine. Langston was formerly a faculty member at Stanford University and Chairman of Neurology at Santa Clara Valley Medical Center in San Jose, California. Langston has authored or co-authored some 360 peer-reviewed articles in the field of neurology, most of which are on Parkinson's disease and related disorders. Langston gained national and international recognition in 1982 for the discovery of the link between a "synthetic heroin" contaminant (MPTP) and parkinsonism.
Phenoperidine, is an opioid analgesic which is structurally related to pethidine and is used clinically as a general anesthetic.
Ohmefentanyl is an extremely potent opioid analgesic drug which selectively binds to the µ-opioid receptor.
(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine is lacking the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.
Prodine is an opioid analgesic that is an analog of pethidine (meperidine). It was developed in Germany in the late 1940s.
Allylprodine is an opioid analgesic that is an analog of prodine. It was discovered by Hoffman-La Roche in 1957 during research into the related drug pethidine. Derivatives were tested to prove the theory that phenolic and non-phenolic opioids bind at different sites of the opiate receptor.
Piminodine (Alvodine) is an opioid analgesic that is an analogue of pethidine (meperidine). It was used in medicine briefly during the 1960s and 70s, but has largely fallen out of clinical use. It was used particularly for obstetric analgesia and in dental procedures and, like pethidine, could be combined with hydroxyzine to intensify the effects. The duration of action is 2–4 hours; 7.5–10 mg via the subcutaneous route is the most common starting dose, being equal to 80–100 mg of pethidine, 40–60 mg of alphaprodine and 10 mg of morphine. Oral formulations were also available.
Propiram is a partial μ-opioid receptor agonist and weak μ antagonist analgesic from the ampromide family of drugs related to other drugs such as phenampromide and diampromide. It was invented in 1963 in the United Kingdom by Bayer but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached Phase III clinical trials in the United States and Canada.
Phenampromide is an opioid analgesic from the ampromide family of drugs, related to other drugs such as propiram and diampromide. It was invented in the 1960s by American Cyanamid Co. Although never given a general release, it was trialled and 50 mg codeine ≈ 60 mg phenampromide. Tests on the 2 isomers showed that all of the analgesic effects were caused by the (S) isomer. Introduction of a phenyl group to the 4-position of the piperidine-ring produces a drug 60-fold more potent than morphine. The most potent reported derivative is 4-hydroxy-4-phenyl phenapromide which displays analgesic activity some x150 greater than morphine.
PEPAP (phenethylphenylacetoxypiperidine) is an opioid analgesic that is an analog of desmethylprodine.
MPP+ (1-methyl-4-phenylpyridinium) is a positively charged organic molecule with the chemical formula C12H12N+. It is a neurotoxin that acts by interfering with oxidative phosphorylation in mitochondria by inhibiting complex I, leading to the depletion of ATP and eventual cell death.
Allylnorpethidine (WIN-7681) is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine (meperidine).
Befiradol is an experimental drug being studied for the treatment of levodopa-induced dyskinesia. It is a potent and selective 5-HT1A receptor full agonist.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
UWA-101 is a phenethylamine derivative researched as a potential treatment for Parkinson's disease. Its chemical structure is very similar to that of the illegal drug MDMA, the only difference being the replacement of the α-methyl group with an α-cyclopropyl group. MDMA has been found in animal studies and reported in unauthorised human self-experiments to be effective in the short-term relief of side-effects of Parkinson's disease therapy, most notably levodopa-induced dyskinesia. However the illegal status of MDMA and concerns about its potential for recreational use, neurotoxicity and potentially dangerous side effects mean that it is unlikely to be investigated for medical use in this application, and so alternative analogues were investigated.
LS-115509 is an opioid analgesic related to the 4-phenylpiperidine family. It is comparable to drugs such as prodine and pheneridine, but is distinguished by the presence of an ether group and furan ring at the piperidine 4-position, which are not found in other drugs of this class. In animal studies, it has around 2-3x the potency of morphine depending on what assay is used. Like prodine, it has two stereocenters and four possible enantiomers, but the activity of these has not been tested separately.
OPPPP is one of several compounds derived from MPPP, the reversed ester of the opioid analgesic pethidine, which were sold as designer drugs in the 1980s, but have been rarely encountered by law enforcement since the passage of the Federal Analogue Act in 1986. In animal studies it was found to be around 1000× the potency of pethidine, making it several times the potency of fentanyl and with similar hazards of respiratory depression and overdose. It is closely related to numerous compounds made by Janssen et al. for which the structure-activity relationship is well established.
