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Wyoming has had a formal partnership with the African country of Tunisia since Casey Henry, commander of the 84th CST. The Wyoming National Guard will benefit from this training by identifying violent extremist organizations and their regional capabilities. Both parties build a trusting and productive relationship and share best practices. The partnership significantly benefits the stabilization of a legitimate military in northern Africa, where Tunisia has one of the few viable democracies. Pritchett was in Tunisia observing the training. Members have the skills and equipment to identify CBRN substances, assess current and projected threats, advise on response measures, and assist with procuring additional resources. Skip to main content Press Enter. Published Aug.

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Official websites use. Share sensitive information only on official, secure websites. Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, ie, aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine, in the case of three drugs, ie, potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, ie, iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought. The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck. Keywords: chloral hydrate, chlorpromazine, imipramine, iproniazid, lithium, lysergic acid diethylamide, meprobamate, penicillin, serendipity, sildenafil. Serendip is the old Arabic name for Ceylon, nowknown as Sri. No scientific discovery has ever been made by pure luck. Perkins' discovery cannot, be attributed to pure luck. He studied at, the Royal College of Chemistry in London under August Wilhclm von Hofmann , one of the pioneers of aniline chemistry, 16 and was aware that crystalline a substance obtained by O. Unverdorben in by distillation of indigo and kyanol or cyanol a substance isolated from coal tar by K Runge in , that produced a beautiful blue color on treatment with calcium chloride , were the same substance phenylamine, with the composition of C 5 H 5 NH 2 that C. Fritzsche obtained by treating indigo with potassium chloride, and named aniline. He was also fully aware of the potential use of his discovery. The introduction of the first, effective drugs for the control of excitement, agitation, and insomnia paralleled the birth of the pharmaceutical industry. In the clinical development, of at least two of these drugs, potassium bromide and chloral hydrate, serendipity played an important role. Potassium bromide is the oldest widely used sedative in medicine. It, is the potassium salt of bromine, a chemical element, first isolated in from the ashes of seaweed by A. Balard, an apothecary in Montpelicr, France. As a, potassium salt it is well tolerated. French clinicians believed that bromine was a substitute for iodine, and began using potassium bromide in a variety of disorders without tangible therapeutic effect. In , 31 years after bromine was isolated, Charles Lockock, a London internist, discovered the anticonvulsant and sedative action of the drug. Lockock, like most physicians of his time, believed that there was a, cause-effect relationship between masturbation, convulsions, and epilepsy. Bromides were known to curb the sex drive. Lockock's rationale was to control epilepsy, ie, convulsions, by reducing the frequency of masturbation. It also brought to attention the sedating properties of the drug. During the second half of the 19th century, potassium bromide and other inorganic bromide salts were widely used as anxiolytic sedatives and anticonvulsants. Similar to potassium bromide, the discovery of the sedative and hypnotic properties of chloral hydrate was also the result, of an erroneous idea, but, in this case of a, chemical theory. Chloral, or trichloroacetaldchydc, was first, prepared in by Justus von Liebig, a professor of chemistry in Giessen Germany. Although no chloroform resulted from the degradation of chloral hydrate, chloral hydrate became the first synthetically produced reliable hypnotic; today, after almost, years, it is still used in clinical practice. This discovery and rediscovery of the therapeutic effects of lithium in psychiatry were the result, of false theories about, the etiology of mood disorders. Lithium is an alkali metal that, was discovered by J. Arfvedson in while analyzing the mineral petalite. Bunsscn and A. Mathiesscn, in Four years later, after the demonstration that lithium carbonate could dissolve urate stones, 27 the substance was introduced into medicine for the treatment of gout by Alfred Barring Garrod. In the late s the therapeutic effect of lithium in mania was rediscovered by John Cade, an Australian psychiatrist. To test, this hypothesis he compared the effects of intraperitoneally injected concentrated urine from manic subjects with urine from normal, subjects in guinea pigs, and found the former far more toxic in killing the animals than the latter. Since the urine of manic patients was more toxic than could be neutralized by the protective action of creatinine, he decided to determine the toxicity-enhancing effect of uric acid. Because uric acid was virtually insoluble in water, he used the most soluble of the urates, lithium urate, in his experiments. To his surprise, instead of enhancing toxicity, lithium urate protected the animals from urea's toxic effects. To determine whether lithium salts alone have any discernable effects, Cade injected large doses of 0. It may seem a long way from the lethargy of guinea pigs to the control of manic excitement, but, since Cade's investigations had commenced in an attempt to demonstrate the presence of a toxic substance excreted in the urine of manic patients, he decided to compare the effect of lithium in ten manic, six schizophrenic, and five depressed patients. The substance was effective in controlling psychotic excitement, especially in manic patients. Cade's rediscovery of the therapeutic effect of lithium in mania, led to systematic clinical investigations with the substance in the s by Mogens Schou and his associates in Denmark, verifying the therapeutic effect of lithium in mania, 35 and rediscovering in the s its prophylactic effect in manic-depressive psychosis and recurrent depression. Cade's notion that mania is the manifestation of a toxic agent, was in keeping with contemporary thinking about the biology of psychoses. One of the strong influences on the Zeitgeist was Rolv Gjcssing's discovery in the mid of nitrogen retention in certain phases of periodic catatonia, 38 and his postulation that, altered metabolism with the production of a mescaline-like substance was responsible for catatonia. D , a synthetic amide of the ergot alkaloid, lysergic acid, 40 in the early s. Ergot is a biological product of a growing fungus, Claviceps purpura, which had been used by women for inducing contractions of the uterus since the Middle Ages. It was introduced into medicine as a uterotonic by an American physician John Stearns in It led to the first partial synthesis of a natural ergot alkaloid, ergometrine, a uterotonic, and, by modifying the alkanolamine side chain of ergometrine, to a synthetic ergot derivative, methergine, a hemostatic. In , Hofmann, working in the laboratories of Sandoz, prepared lysergic acid diethylamide, a, substance structurally related to the circulatory stimulant, nikethamide, with the objective of developing an analeptic. Since the substance was the 25th compound of the lysergic acid amide series, it was given the code name LSD 43 In pharmacological testing LSD produced uterine contraction, similar to that of ergometrine. Fixcitation was observed in some animals after LSD administration. The findings did not, warrant immediate further exploration. On April 16, , while preparing a new supply of LSD, Hofmann was struck by a strange feeling that made him stop work in the mid-afternoon. He reported the following to his superior:. I was seized by a peculiar restlessness associated with a sensation of mild dizziness. On arriving home I lay down and sunk into a kind of drunkenness which was not unpleasant and which was characterized by extreme activity and imagination. As I lay in a dazed condition with my eyes closed I experienced daylight as disagreeably bright there surged upon me an uninterrupted stream of fantastic images of extraordinary plasticity and vividness and accompanied by the intense, kaleidoscopic play of colors. The condition gradually passed off after about two hours. Since he took relatively high doses of the substance, the psychotomimetic effects were even more pronounced than on the first occasion. In the mids, demonstration of the therapeutic effect of penicillin in primary syphilis and neurosyphilis with its implications for psychiatry distracted attention from Hofmann's discovery. It, was more than 10 years later in the early s that interest, in LSD was revived after Woolley and Shaw's demonstration that it inhibited the neurotransmitter serotonin. The serendipitous discovery of penicillin in by Alexander Fleming led to major changes in the diagnostic distribution of psychiatric patients in the late s. Fleming was engaged in research on influenza when one of his staphylococcus culture plates had become contaminated and developed a, mold that created a, bacteria-free circle. However, Fleming recognized the possible significance of the bacteria-free circle, 45 and by isolating the mold in pure culture he found that it, produced a substance that has a powerful destructive effect on many of the common bacteria that infect man. Although Fleming published his results in the Journal of Experimental Pathology in , 44 it was only 10 years later that Howard Florey and his team embarked on the research that culminated in in the development of a methodology for the extraction and production of penicillin. To obtain sufficient, quantity of the substance for clinical use, the original strain, Penicillium notatum, had to be replaced by Penicillium chrysogenum. The introduction of penicillin stimulated the industry to develop other antibiotics. The development of meprobamate, the first anxiolytic drug introduced into clinical practice, was the result of a, serendipitous observation in the course of this research. Chemists were to develop nontoxic antibacterial agents that would inhibit the growth of Gram-negative micro-organisms that cause enzymatic destruction of penicillin. Berger moved to the United States in , and in the same year mephenesin was released for clinical use for muscular relaxation during light anesthesia, under the trade name Tolserol by E. The drug was already in clinical use when it, was recognized that it, could relieve anxiety and tension. However, mephenesin had serious drawbacks, eg, short, duration of action and greater effect on the spinal cord than on supraspinal structures. To overcome these disadvantages, Berger succeeded in initiating a program that yielded the synthesis of meprobamate, or 2-methyln-propyl-l,3-propanediol dicarbamate, by B. Similar to mephenesin, pharmacologically meprobamate was a tranquilizer. It depressed multineuronal reflexes without significantly affecting monosynaptic reflexes; counteracted pentylenetetrazol-induced convulsions, and produced a loss of the righting reflex in mice without causing significant excitement prior to the onset of the paralysis. In the spring of Lowell Selling was first to report on the therapeutic effect of meprobamate in anxiety and tension states. A few months later, in the summer of , meprobamate was introduced into clinical use by Wallace Laboratories with the brand name of M'iltown,the name of the small community in New Jersey where Berger lived at, the time, 52 and by Wyeth Laboratories with the brand name of Equanil. By the late s meprobamate was the most widely used prescription drug in the United States and in many other countries. It retained its lead until the late s when it succumbed to diazepam, the second drug from the benzodiazepine series introduced into clinical use. In the early s Sternbach was a postgraduate student at the Jagellonian University in Cracow, Poland, and synthesized several, heptoxdiazine compounds in an effort to develop synthetic dyes. In , inspired by the phenomenal success of chlorpromazine and early reports on meprobamate, he resumed his research with heptoxdiazines with the hope of finding compounds with psychopharmacological activity. Although all of the newly synthesized drugs that were tested were pharmacologically inert, Sternbach decided to stabilize one of the benzoxadiazepines with methylamine, a primary amine, instead of using secondary or tertiary amines as in the pharmacologically inert derivatives. He labeled the stabilized compound Ro , and placed it, on the shelf. In , Ro 5- was found, literally during a, laboratory cleanup, and submitted for pharmacological evaluation, which showed that it had similar activities to meprobamate. This was sheer luck! Prompted by these findings, the structure of Ro was correctly identified as 1,4-benzodiazepine. Ro , the first anxiolytic benzodiazepine, was introduced into clinical use in with the generic name of methaminodiazepoxide chlordiazepoxide , and the brand name of Librium. It was followed by the introduction of diazepam Valium , another anxiolytic benzodiazepine, in From the late s through the s, sales of diazepam topped those of all other drugs in the United States. The introduction of benzodiazepines vastly extended the use of psychotropic drugs, ranging from the treatment of schizophrenia, depression, and bipolar disorder to the alleviation of anxiety and other neurotic conditions, making psychotropic drugs one of the most, prosperous businesses of the pharmaceutical industry. During the s, a scries of new psychotropic drugs, such as chlorpromazine, imipramine, and iproniazid, were introduced. Their effectiveness in the treatment of schizophrenia, depression, and bipolar disorder was instrumental in shifting the site of psychiatric practice from psychiatric hospitals to the community. Chlorpromazine CPZ , has a phemothiazine nucleus with a dimethylaminopropyl side chain. The basic phenothiazine nucleus was synthesized by Bernthsen in , and later introduced as an anthelminthic agent for the treatment, of enterobiasis. Expectations that it might be effective in the treatment of protozoal infections were not fulfilled. Instead, Henri Laborit, a surgeon in the French Navy, at the Bizerte Naval Hospital in Sidi-Abdallah, Tunisia, found promethazine, one of the antihistaminic phenothiazines synthesized in the early s, to be eminently suited for the prevention of surgical shock. In Laborit. In he received a supply of CPZ for his clinical investigations. In February Laborit, in collaboration with Huguenard and Alluaume, reported that in doses of 50 to mg intravenously, CPZ does not cause loss of consciousness or any change in the patient's mentation, but produces a, tendency to sleep and disinterest in the surroundings. Val de Grace, the military hospital in Paris, in March , about a, month after the report of Laborit. Subsequently, within a short, period of 3 years, from to , CPZ treatment in psychiatry spread around the world. The first international colloquium on the therapeutic uses of CPZ in psychiatry was held in Paris, in October, , with participants from 15 countries. Lehmann, from Canada, for bringing the full practical significance of CPZ to the attention of the medical community. In the same year Daniel Bovet was awarded the Nobel Prize in Medicine for his major contributions to the synthesis of antihistamines which, through Laborit's serendipitious discovery that an antihistaminic phenothiazine, promethazine, produced a, state of detachment and indifference, led to the development of CPZ. TTtic serendipitous discovery of the therapeutic effect of imipramine in depression was the result of search for a CPZ-like substance for the treatment, of schizophrenia by Geigy, at the time a major Swiss pharmaceutical company. The basic constituent, G 22,, is the iminodibenzyl nucleus, synthesized in by Thiele and Holzinger. Kuhn's expectations were not fulfilled. The substance was ineffective in schizophrenia. Nonetheless, before returning his drug supply, Kuhn decided to try the substance in one of his female patients with severe endogenous depression. This led to the recognition on January 18,, that G 22, may have antidepressant, effects. Encouraged by his findings, Kuhn administered G 22, to two more female patients with severe endogenous depression. In both patients the drug had favorable effects. Furthermore, in all three patients discontinuation of treatment resulted in relapse, which was reversed by resumption of the medication. This prompted Kuhn to treat 40 more depressed patients with G 22, at the clinic. It, was on the basis of his observations of these patients that he concluded that the drug is effective in endogenous depression, in which vital disturbance is in the foreground. Kuhn's first, paper on the treatment, of depressive states with an iminobenzylderivative, G 22, was published in the August 31st issue of the Swiss Medical Journal in By the end of the year, G 22,, the first tricyclic antidepressant, was released for clinical use in Switzerland with the generic name of imipramine, and the brand name of Tofranil. There was strong opposition by academic psychiatry to the drug treatment of depression in the late s, but Kuhn prevailed, and the introduction of imipramine opened up the path for the development, of other antidepressants. In the same year that Kuhn presented and published his findings on the antidepressant effect of imipramine, two independent groups of investigators, Loomers, Saunders, and Kline, and Crane, presented their findings on the therapeutic effect, of iproniazid, a monoamine oxidase inhibitor, in depression, at a, regional meeting of the American Psychiatric Association in Syracuse, New York. In , using iproniazid in tubercular patients, Sclikoff, Robitzek, and Orcnstein noted that, the drug produced euphoria and overactive behavior in some patients. Monoamine oxidase MAO is the enzyme responsible for the oxidative deamination of neurotransmitter monoamines, such as serotonin 5-H. T and norepinephrine NE. The presence of these substances in the brain was first shown in and respectively; and the instrument, spectrophotofluorimeter ,with a, resolution power to measure the concentration of these monoamines and their metabolites in the brain, was introduced in The combination of serendipity and science that led to the development of MAO inhibitors for the treatment of depression triggered the development of neuropsychopharmacology. In the current, psych opharmacological era in psychiatry, the scope of psychiatry is extended to dimensional anomalies of abnormal psychology. Ever-newer drugs for multiplying indications are introduced, and in the development of at least one of these new drugs, sildenafil, serendipity has played a role. Sildenafil is a selective 5-phosphodiesterase inhibitor that dilates cardiac vessels by acting on cyclic-GMP. However, expectations in clinical investigations with sildenafil in the treatment of angina pectoris conducted by Pfizer, one of the major American pharmacological companies, were not fulfilled. Instead of relieving anginal pain, the drug induced unwanted penile erections in some patients. Independently of Pfizer, Solomon Snyder and his associates at, Johns Hopkins University were working with nitric oxide NO , a, substance responsible for the physiological relaxation of blood vessels. In the course of this research they found that NOS is localized in the penis; demonstrated that erections are blocked by NOS inhibitors, and suggested that NO is the transmitter of penile erection. Shifting the direction of clinical investigations with sildenafil from angina, pectoris to erectile dysfunction led to the demonstration of the effectiveness of the drug in the treatment, of male erectile disorder Diagnostic and Statistical Manual of Mental Disorders, 4th ed - DSM - IV 37 , and to the marketing of sildenafil with the brand name of Viagra. Serendipity is one of the many contributing factors to drug discovery. It, has certainly played a, role in the discovery of most of the prototype psychotropic drugs. The discovery process includes the recognition of the potential of the findings on the basis of one's knowledge and past, experience. As a library, NLM provides access to scientific literature. Dialogues Clin Neurosci. Show available content in en es fr. Find articles by Thomas A Ban. Issue date Sep. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. 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