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Cognitive dysfunction and dementia
Published in Ad (Sandy) Macleod, Ian Maddocks, The Psychiatry of Palliative Medicine, 2018
Ad (Sandy) Macleod, Ian Maddocks
Dementia is a chronic and progressive clinical syndrome characterised by an acquired impairment of three domains of function: neuropsychological (amnesia, aphasia, apraxia, agnosia, executive dysfunction), behavioural/psychological (or more correctly psychiatric) symptoms (BPSD), and deficits in activities of daily living (ADL) (sufficient to interfere with occupational performance and social interactions). Dementia is distinguished from mental retardation by its acquired nature. Demented persons are at high risk of delirium because of a low deliriant threshold (seeChapter 9). Amnestic syndromes and aphasia are more focal impairments. Depressive pseudodementia can mimic dementia, but the history usually provides differentiation. These patients, unlike those with dementia, complain of poor memory and provide ‘don’t know’ (can’t be bothered) answers to routine questions. A normal shedding of interest in current world events as terminal illness enters its final phase can be mistaken for the apathy and disinterest of dementia. In benign senile forgetfulness (or mild cognitive impairment), the deficits are predominantly slowing of performance, and are non-progressive. Reversible causes of dementia are rare. The commonest type of dementia is AD (60%) followed by vascular dementia (VD) (20%). Dementia with Lewy bodies (DLB) accounts for 15%, and frontotemporal dementia (FTD) 5% (see Table 12.2).
Where do we go next in antidepressant drug discovery? A new generation of antidepressants: a pivotal role of AMPA receptor potentiation and mGlu2/3 receptor antagonism
Published in Expert Opinion on Drug Discovery, 2022
Andrzej Pilc, Agata Machaczka, Paweł Kawalec, Jodi L. Smith, Jeffrey M. Witkin
The structures of two muscarinic receptor antagonists that have clinical use in patients are shown in Figure 5. Biperiden is used in the clinical management of Parkinson’s disease [80]. Both scopolamine and biperiden have been studied for their antidepressant effects with scopolamine being the most widely investigated in depressed patients. Scopolamine is a naturally derived alkaloid of a species of plant from the Solanaceae family. Scopolamine is a nonselective antagonist of muscarinic acetylcholine receptors and is widely used as a butyl bromide salt in the treatment of abdominal pain, irritable bowel syndrome and bladder spasms (in this form it does not readily penetrate into the CNS). A hydrobromide derivative (which enters the brain) is used as a motion sickness reliever and sometimes as a preoperative medication [81]. Scopolamine induces hyperactivity and dream-like ‘hallucinations,’ and at a dose of 24 ug/kg i.m., produced delirium in humans [82]. Scopolamine belongs to a separate group of drugs that have been termed deliriants [83].
Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions
Published in International Review of Psychiatry, 2018
Albert Garcia-Romeu, William A. Richards
The term hallucinogen is applied broadly to many different naturally occurring and synthetic drugs with various mechanisms of action and profiles of subjective effects (Garcia-Romeu, Kersgard, & Addy, 2016; Nichols, 2004). These may include the psychedelics such as lysergic acid diethylamide (LSD), psilocybin, mescaline, and dimethyltryptamine (DMT), whose primary psychoactive effects are largely mediated by their activity at serotonin, and particularly serotonin 2A (5-HT2A), receptors (Glennon, Titeler, & McKenney, 1984; Nichols, 2016; Vollenweider, Vollenweider-Scherpenhuyzen, Bäbler, Vogel, & Hell, 1998); the entactogens such as 3,4-Methylenedioxy-methamphetamine (MDMA), which stimulate release of serotonin, dopamine, and norepinephrine, and inhibit their reuptake (Nichols, 1986; Nichols & Oberlender, 1990); the dissociative anaesthetics that exert their main effects via glutamatergic N-Methyl-D-Aspartate (NMDA) receptor antagonism (Krystal et al., 1999; Morris & Wallach, 2014); and atypical hallucinogens such as ibogaine (Popik, Layer, & Skolnick, 1995), the kappa opioid receptor agonist salvinorin A (Addy, 2012; Johnson, MacLean, Reissig, Prisinzano, & Griffiths, 2011), anticholinergic deliriants such as Datura (Forrester, 2006), and cannabinoids (Keeler, Ewing, & Rouse, 1971). The focus of this article is on psychedelic therapy involving administration of 5-HT2A agonist psychedelics, as opposed to other hallucinogens, whose pharmacological and potential therapeutic mechanisms differ sufficiently to distinguish them from the current topic.1
Novel psychotherapeutics – a cautiously optimistic focus on Hallucinogens
Published in Expert Review of Clinical Pharmacology, 2018
Alexander M. Sherwood, Thomas E. Prisinzano
‘Hallucinogens,’ in a general sense, define a vast and diverse set of molecules that elicit significant alteration in human consciousness by acting on targets in the central nervous system, temporarily rerouting synaptic transmission in the brain. Commonly accepted classes of hallucinogens include psychedelics, entactogens, dissociatives, and atypical hallucinogens that include deliriants, cannabinoids, and kappa opioids. Each class possesses its own unique attributes and subclasses as well as some degree of overlap with regard to perceived effects, pharmacology, and/or potential therapeutic utility [2].