A Biochemical and Pharmacological Suggestion About Certain Mental Disorders

Woolley, D. W.; Shaw, Elliott

doi:10.1073/pnas.40.4.228

Cited by 503 publications

(153 citation statements)

References 11 publications

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“…Indeed, the early finding that LSD blocks the action of serotonin in smooth muscle (Gaddum 1953;Wooley and Shaw 1954) more than 40 years, we still cannot explain why LSD has such potent and profound effects on perception, mood, and thought processes. Of the many subtypes of serotonin receptors, the action of LSD at the 5-HT 2 family of G-protein-coupled receptors has been most convincingly implicated in the behavioral effects of LSD and other hallucinogenic agents (Titeler et al 1988).…”

Section: For More Than 40 Years the Hallucinogen Lysergic Acid Diethymentioning

confidence: 94%

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Agonist-Directed Signaling of Serotonin 5-HT2C Receptors Differences Between Serotonin and Lysergic Acid Diethylamide (LSD)

Backstrom

Chang

Chu

et al. 1999

Neuropsychopharmacology

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For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HTThe serotonin receptor superfamily is composed of 14 members to date which have recently been re-classified based on gene structure, amino acid sequence homology, and intracellular signaling cascades (Hoyer et al. 1994). All but one (5-HT 3 ) of the serotonin receptors couples to G proteins, producing second messengers that regulate cellular functions via phosphorylation/ dephosphorylation of intracellular proteins. The five families of G-protein-coupled receptors (5-HT 1 , 5-HT 2 , 5-HT 4 , 5-HT 5 , and 5-HT 7 ) regulate the two major intracellular second messenger pathways, adenylate cyclase and phospholipase C (for review see Sanders-Bush and Canton 1995). The 5-HT 2 receptor family is composed of three subtypes (5-HT 2A , 5-HT 2B , and 5-HT 2C ) linked via the Gq/11 family of G proteins to activation of phospholipase C with the generation of two second messengers, IP 3 which releases intracellular stores of calcium, and diacylglycerol, which activates protein kinase C. Recently, it has become clear that the 5-HT 2 receptor family also has the ability to activate other intracellular signaling pathways. For example, the 5-HT 2C receptor has been shown to activate phospholipase A 2 (Berg et al. 1996), regulate adenylate cyclase (Lucaites et al. 1996) and increase cyclic GMP (Kaufman et al. 1995). Whether these various signaling pathways are parallel or converging is not yet known, nor is it known what are the relative contribution of these pathways to in vivo function of 5-HT 2C receptors in choroid plexus epithelia and neurons.The ergoline hallucinogenic drug lysergic acid diethylamide (LSD) binds with high affinity to serotonin receptors. Indeed, the early finding that LSD blocks the action of serotonin in smooth muscle (Gaddum 1953;Wooley and Shaw 1954) more than 40 years, we still cannot explain why LSD has such potent and profound effects on perception, mood, and thought processes. Of the many subtypes of serotonin receptors, the action of LSD at the 5-HT 2 family of G-protein-coupled receptors has been most convincingly implicated in the behavioral effects of LSD and other hallucinogenic agents (Titeler et al. 1988). LSD behaves as a partial agonist at 5-HT 2A (Burris et al. 1991;Marek and Aghajanian 1996) and 5-HT 2C receptors (Sanders-Bush et al. 1988;Egan et al. 1998). Because of its partial agonist proterties, LSD has the potential to partially block the effect of serotonin. It is possible that this 5-HT 2A/2C receptor partial agonist property explains the unique behavioral properties of LSD; however, other partial agonists at 5-HT 2A/2C receptors, such as m-CPP and lisuride, do not produce LSD-like behavior in humans (Grotewiel et al. 1994;Titeler et al. 1988). Therefore, there must be something unique about LSD versus serotonin that is re...

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Section: For More Than 40 Years the Hallucinogen Lysergic Acid Diethymentioning

confidence: 94%

“…Indeed, the early finding that LSD blocks the action of serotonin in smooth muscle (Gaddum 1953;Wooley and Shaw 1954) fueled interest in brain serotonin. Although LSD has been linked to serotonin for more than 40 years, we still cannot explain why LSD has such potent and profound effects on perception, mood, and thought processes.…”

mentioning

confidence: 99%

Agonist-Directed Signaling of Serotonin 5-HT2C Receptors Differences Between Serotonin and Lysergic Acid Diethylamide (LSD)

Backstrom

Chang

Chu

et al. 1999

Neuropsychopharmacology

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“…Although the underlying etiology of schizophrenia is still poorly understood, lines of evidence suggest that dysfunction in 5‐hydroxytryptamine (serotonin) processes involves in the pathophysiology of schizophrenia (Ellenbroek & Prinssen, 2015; Wooley & Shaw, 1954). Furthermore, another evidence is that the serotonin system plays a critical role in the efficiency of second generation antipsychotics, though binding much strongly with the serotonin system than dopamine system (Lieberman et al., 1998).…”

Section: Introductionmentioning

confidence: 99%

Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

et al. 2017

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IntroductionThe relationship between peripheral 5‐HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown.MethodsA total 52 first‐episode and drug‐naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week.ResultsThere was no difference in 5‐HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline (p = .24). Among 47 patients who completed 8‐week naturalistic follow‐up, 37 were responders to risperidone treatment. 5‐HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8‐week treatment with risperidone (p = .29). However, 5‐HT3A receptor mRNA level in responders increased significantly (p = .04), but not in nonresponders (p = .81).ConclusionsSuccessful treatment with risperidone increases 5‐HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5‐HT3A receptor may be involved in the mechanism of risperidone effect.

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“…These compounds, which each contain an indole nucleus, are antagonists of 5-hydroxytryptamine (Shaw & Woolley, 1953) and may cause psychic disturbances (Iberico, 1941;Woolley & Shaw, 1954). Each was practically without effect on cortical neurones.…”

Section: Conhch(c2h5)ch20h --(+) Slowmentioning

confidence: 99%

Actions of Certain Amines on Cerebral Cortical Neurones

Krnjević

Phillis

1963

British Journal of Pharmacology and Chemotherapy

202

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A number of derivatives of tryptamine and phenethylamine, and certain other compounds, were tested on neurones in the cerebral cortex of cats by iontophoretic release from micro-pipettes. The characteristic action of many of these compounds was a depression of the neuronal discharge initiated by synaptic activity or by the application of L-glutamate; imidazolylacetic acid, dopamine, ephedrine and ergometrine were particularly effective. Catechol amines, hydroxytryptamines and imidazolylacetic acid had a relatively quick and rapidly reversible action, not unlike that of y-aminobutyric acid, whereas ephedrine and derivatives of lysergic acid diethylamide caused a slower and more prolonged depression of the amplitude of spikes, rather like atropine. Several compounds, including 5-hydroxytryptamine, adrenaline and ergometrine, could also excite the same neurone when larger amounts were applied. A few substances, such as dopa and methylergometrine, had a predominantly excitant action.There has been much speculation during the course of the last decade concerning the significance of several indole and catechol amines which occur naturally in the brain. Interest in these substances has increased as a result of recent developments in the study of psychotropic compounds, some of which are structurally related to the indole and catechol amines (lysergic acid diethylamide, bufotenine, mescaline and others).Evaluation of the importance of these compounds in central nervous mechanisms (Marrazzi & Hart, 1955;Marrazzi, 1957). These findings were substantiated by Ochs, Booker & Aprison (1960), who showed that 5-hydroxytryptamine, applied topically, depressed cortical responses to direct stimulation;

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A Biochemical and Pharmacological Suggestion About Certain Mental Disorders

Cited by 503 publications

References 11 publications

Agonist-Directed Signaling of Serotonin 5-HT2C Receptors Differences Between Serotonin and Lysergic Acid Diethylamide (LSD)

Agonist-Directed Signaling of Serotonin 5-HT2C Receptors Differences Between Serotonin and Lysergic Acid Diethylamide (LSD)

Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

Actions of Certain Amines on Cerebral Cortical Neurones

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