piperidines and Intellectual-Disability

At present, there may be over 210,000 people with Down syndrome (DS) over the age of 55 in the United States (US) who have significant needs for augmented services due to circumstances related to ordinary and/or pathological aging. From 1979 through 2003, the birth prevalence of DS rose from 9.0 to 11.8 (31.1%) per 10,000 live births in 10 representative US regions. This increase, largely due to women conceiving after age 35, portends an ever-growing population of people with DS who may be subject to pathogenic aging. Whereas Trisomy 21 is one of the most widespread genetic causes of intellectual disability (ID), it still is one of the least understood of all genetic ID syndromes. While longevity in people with DS has improved appreciably in as modest a period as 30 years, age-specific risk for mortality still is considerably increased compared both with other people with ID or with the typically developing population. The penetrance of the phenotype is widely distributed, even though a consistent genotype is assumed in 95% of the cases. Some, but not all body systems, exhibit signs of premature or accelerated aging. This may be due to both genetic and epigenetic inheritance. We now know that the long-term outcome for people with DS is not as ominous as once contemplated; a number of people with DS are living into their late 60s and 70s with few if any major signs of pathogenic aging. Alzheimer's disease (AD), a devastating disease that robs a person of their memory, abilities and personality, is particularly common in elder adults with DS, but is not a certainty as originally thought, some 20% to 30% of elder adults with DS might never show any, or at most mild signs of AD. DS has been called a mature well-understood syndrome, not in need of further research or science funding. We are only beginning to understand how epigenetics affects the phenotype and it may be feasible in the future to alter the phenotype through epigenetic interventions. This chapter is divided into two sections. The first section will review typical and atypical aging patterns in somatic issues in elder adults with DS; the second section will review the multifaceted relationship between AD and DS.

Topics: Adult; Aging; Alzheimer Disease; Amyloid beta-Peptides; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Female; Humans; Incidence; Indans; Intellectual Disability; Male; Metabolic Syndrome; Middle Aged; Nootropic Agents; Oxidative Stress; Peptide Fragments; Phenotype; Piperidines; Prevalence; Telomere Shortening; Treatment Outcome; United States

Topics: Adolescent; Adult; Aged; Alcoholism; Antisocial Personality Disorder; Child; Dementia; Epilepsy; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Neurotic Disorders; Nitriles; Paranoid Disorders; Personality Disorders; Phenothiazines; Piperidines; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

To compare two remifentanil doses (1 µg/kg and 2 µg/kg) in order to determine the preferred dose in intellectually disabled patients undergoing day care dental surgery under sevoflurane-induced general anaesthesia.. Patients were randomly assigned to receive either 1 µg/kg (group 1) or 2 µg/kg (group 2) remifentanil; both groups received 8% sevoflurane anaesthesia induction. All other conditions were identical in both groups. Heart rate (HR), mean arterial pressure (MAP) and intubation conditions were assessed.. A total of 27/30 (90.0%) patients in group 1 and 29/30 patients (96.7%) in group 2 had acceptable intubation conditions. Remifentanil administration resulted in significant reductions in HR compared with baseline levels, in both groups. There were no significant between-group differences in HR at any timepoint. MAP decreased significantly compared with baseline in group 2 only.. Successful tracheal intubation in intellectually disabled patients can be accomplished with a combination of 1 µg/kg or 2 µg/kg remifentanil and 8% sevoflurane anaesthesia induction, without the requirement for neuromuscular blocking drugs.

Topics: Adolescent; Adult; Analgesics, Opioid; Anesthesia, Dental; Anesthetics, Inhalation; Arterial Pressure; Child; Drug Administration Schedule; Drug Combinations; Female; Heart Rate; Humans; Intellectual Disability; Intubation, Intratracheal; Male; Methyl Ethers; Piperidines; Remifentanil; Sevoflurane

A double-blind placebo-controlled cross-over trial was carried out to evaluate the efficacy and safety of the combined serotonin-dopamine antagonist risperidone in mentally retarded patients with persistent behavioural disturbances. After an observation period of 1 week, risperidone 4-12 mg or placebo was administered during 3 weeks as add-on treatment to the existing medication, followed by a 1-week single-blind placebo wash-out, and another 3 weeks of double-blind treatment with the cross-over medication. Thirty-seven patients participated in the trials; 30 completed the study. Risperidone was significantly superior to placebo in its effect on the Aberrant Behaviour Checklist and the Clinical Global Impression. The Extrapyramidal Symptom Rating Scale did not show any differences between risperidone and placebo. Two patients experienced hypotension at the start of the risperidone administration. Sedation and drowsiness were the most frequently reported treatment-emergent adverse events. The results of this trial warrant further investigation into the therapeutic assets of risperidone in this indication, as add-on therapy and as monotherapy.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Isoxazoles; Male; Mental Disorders; Middle Aged; Piperidines; Placebos; Risperidone

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Butyrophenones; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Intellectual Disability; Piperidines; Self Mutilation

Topics: Adolescent; Adult; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Intellectual Disability; Male; Middle Aged; Penfluridol; Piperidines; Psychotic Disorders; Schizophrenia; Tablets; Time Factors

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Dibenzazepines; Drug Evaluation; Enuresis; Female; Humans; Intellectual Disability; Middle Aged; Neurasthenia; Piperidines; Psychotropic Drugs; Schizophrenia

The effectiveness of pericyazine in severe behavioural disorders was evaluated in 15 profoundly and severely retarded children. Pericyazine provided significant improvement in such parameters as co-operation, temper, purposeless activities, hyperactivity, communication and mood. It proved to be statistically superior to the minor tranquillizers in improving co-operation and helpfulness, temper, mood, the understanding of commands and table manners, and in reducing self-abusiveness and abusiveness to staff. The safety of this agent was confirmed and photosensitivity was not found to be associated with its use.

Topics: Adolescent; Analysis of Variance; Child; Clinical Trials as Topic; Female; Humans; Intellectual Disability; Male; Nitriles; Phenothiazines; Piperidines; Placebos; Psychological Tests; Time Factors; Tranquilizing Agents

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Evaluation Studies as Topic; Female; Humans; Hydrocarbons, Halogenated; Injections, Intramuscular; Intellectual Disability; Middle Aged; Piperidines; Schizophrenia; Spiro Compounds; Tranquilizing Agents

Topics: Adult; Aggression; Anticonvulsants; Anxiety; Carbamazepine; Clinical Trials as Topic; Diazepam; Dibenzazepines; Epilepsy; Frustration; Hallucinations; Humans; Intellectual Disability; Middle Aged; Nitriles; Object Attachment; Perceptual Disorders; Phenothiazines; Piperidines; Psychiatric Status Rating Scales; Psychopathology; Schizophrenia; Thiazines; Tranquilizing Agents

In humans a chromosomal hemideletion of the 16p11.2 region results in variable neurodevelopmental deficits including developmental delay, intellectual disability, and features of autism spectrum disorder (ASD). Serotonin is implicated in ASD but its role remains enigmatic. In this study we sought to determine if and how abnormalities in serotonin neurotransmission could contribute to the behavioral phenotype of the 16p11.2 deletion syndrome in a mouse model (Del mouse). As ASD is frequently associated with altered response to acute stress and stress may exacerbate repetitive behavior in ASD, we studied the Del mouse behavior in the context of an acute stress using the forced swim test, a paradigm well characterized with respect to serotonin. Del mice perseverated with active coping (swimming) in the forced swim test and failed to adopt passive coping strategies with time as did their wild-type littermates. Analysis of monoamine content by HPLC provided evidence for altered endogenous serotonin neurotransmission in Del mice while there was no effect of genotype on any other monoamine. Moreover, we found that Del mice were highly sensitive to the 5-HT2A antagonists M100907, which at a dose of 0.1 mg/kg normalized their level of active coping and restored the gradual shift to passive coping in the forced swim test. Supporting evidence for altered endogenous serotonin signaling was provided by observations of additional ligand effects including altered forebrain Fos expression. Taken together, these observations indicate notable changes in endogenous serotonin signaling in 16p11.2 deletion mice and support the therapeutic utility of 5-HT2A receptor antagonists.

Topics: Adaptation, Psychological; Animals; Autistic Disorder; Behavior, Animal; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 16; Disease Models, Animal; Fluorobenzenes; Intellectual Disability; Male; Mice; Piperidines; Receptor, Serotonin, 5-HT2A; Serotonin; Serotonin 5-HT2 Receptor Antagonists; Stress, Psychological

Genetic studies point to a major role of de novo mutations in neurodevelopmental disorders of intellectual disability, autism spectrum disorders, and epileptic encephalopathy. The STXBP1 gene encodes the syntaxin-binding protein 1 (Munc18-1) that critically controls synaptic vesicle exocytosis and synaptic transmission. This gene harbors a high frequency of de novo mutations, which may play roles in these neurodevelopmental disorders. However, the system and behavioral-level pathophysiological changes caused by these genetic defects remain poorly understood. Constitutional (Stxbp1+/-), dorsal-telencephalic excitatory (Stxbp1fl/+/Emx), or global inhibitory neuron-specific (Stxbp1fl/+/Vgat) mice were subjected to a behavioral test battery examining locomotor activity, anxiety, fear learning, and social interactions including aggression. Furthermore, measurements of local field potentials in multiple regions of the brain were performed. Stxbp1+/- male mice exhibited enhanced aggressiveness and impaired fear learning associated with elevated gamma activity in several regions of the brain including the prefrontal cortex. Stxbp1fl/+/Emx mice showed fear-learning deficits, but neither Stxbp1fl/+/Emx nor Stxbp1fl/+/Vgat mice showed increased aggressiveness. Pharmacological potentiation of the excitatory transmission at active synapses via the systemic administration of ampakine CX516, which enhances the excitatory postsynaptic function, ameliorated the aggressive phenotype of Stxbp1+/- mice. These findings suggest that synaptic impairments of the dorsal telencephalic and subcortical excitatory neurons cause learning deficits and enhanced aggression in Stxbp1+/- mice, respectively. Additionally, normalizing the excitatory synaptic transmission is a potential therapeutic option for managing aggressiveness in patients with STXBP1 mutations.

Topics: Aggression; Animals; Brain; Dioxoles; Excitatory Postsynaptic Potentials; Haploinsufficiency; Intellectual Disability; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Munc18 Proteins; Neurodevelopmental Disorders; Neurons; Piperidines; Synapses; Synaptic Transmission

Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability.

Topics: Adult; Ambulatory Care; Anesthesia, Dental; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Anticonvulsants; Benzodiazepines; Clobazam; Clonazepam; Cohort Studies; Delayed Emergence from Anesthesia; Dental Care for Disabled; Female; Follow-Up Studies; Humans; Intellectual Disability; Male; Methyl Ethers; Phenobarbital; Phenytoin; Piperidines; Propofol; Remifentanil; Retrospective Studies; Risk Factors; Sevoflurane; Valproic Acid

Topics: Abnormalities, Multiple; Adolescent; Anesthesia, Intravenous; Anesthetics, Intravenous; Cerebellar Diseases; Cerebellum; Eye Abnormalities; Female; Humans; Intellectual Disability; Kidney Diseases, Cystic; Oral Surgical Procedures; Piperidines; Propofol; Remifentanil; Retina

Topics: Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Bupivacaine; Child, Preschool; Cochlear Implantation; Fentanyl; Growth Disorders; Humans; Intellectual Disability; Laryngeal Masks; Male; Methyl Ethers; Microcephaly; Pacemaker, Artificial; Piperidines; Piroxicam; Remifentanil; Sevoflurane; Syndrome

Topics: Airway Obstruction; Anesthetics, Inhalation; Anesthetics, Intravenous; Failure to Thrive; Fiber Optic Technology; Glaucoma; Humans; Infant; Intellectual Disability; Intubation, Intratracheal; Laryngeal Masks; Male; Maxillofacial Abnormalities; Methyl Ethers; Monitoring, Physiologic; Piperidines; Rare Diseases; Remifentanil; Sevoflurane; Syndrome

Topics: Abnormalities, Multiple; Acidosis; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Atracurium; Blood Gas Analysis; Child, Preschool; Chromosome Disorders; Chromosomes, Human, Pair 9; Female; Fundoplication; Gastroesophageal Reflux; Humans; Intellectual Disability; Intubation, Intratracheal; Laryngoscopy; Methyl Ethers; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Rare Diseases; Remifentanil; Sevoflurane

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Agenesis of Corpus Callosum; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Anticonvulsants; Child; Eye Diseases, Hereditary; Female; Glycopyrrolate; Humans; Intellectual Disability; Laryngoscopy; Midazolam; Nitrous Oxide; Oral Surgical Procedures; Piperidines; Remifentanil; Spasm; Syndrome

To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment.. Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment.. Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently.. Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable.

Topics: Adult; Cholinesterase Inhibitors; Cognition Disorders; Dementia; Donepezil; Down Syndrome; Female; Humans; Indans; Intellectual Disability; Male; Piperidines; Quality of Life

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Atropine; Cleft Palate; Developmental Disabilities; Face; Female; Humans; Infant; Intellectual Disability; Intubation, Intratracheal; Methyl Ethers; Microcephaly; Midazolam; Muscle Hypotonia; Nitrous Oxide; Piperidines; Remifentanil; Sevoflurane; Syndrome

Elevated concentrations of blood serotonin have been documented in autistic children and mentally retarded adults. Antiserotonergic pharmacotherapy has been partially effective in treating a subgroup of children with autistic disorder. Therefore, the possibility is raised that an antiserotonergic treatment may be of value to adult psychiatric patients with a history of pervasive developmental disorder. Two such cases are described where the patients underwent psychiatric and neuropsychological examination before and after treatment with risperidone, a potent 5-HT2 antagonist with additional D2 antagonistic properties. Particular improvements were documented in both patients, despite long histories of cognitive compromise and high likelihood of damage to the central nervous system.

Topics: Adolescent; Adult; Antipsychotic Agents; Autistic Disorder; Child; Child Development Disorders, Pervasive; Follow-Up Studies; Humans; Intellectual Disability; Isoxazoles; Male; Neuropsychological Tests; Piperidines; Risperidone; Serotonin; Stereotyped Behavior

The effects of biperiden and piroheptine on the serum level of zotepine were studied in 15 schizophrenic and 6 mentally retarded in-patients. Neither of these anticholinergic drugs affected the serum level of zotepine nor caused significant side-effects. In the schizophrenics the total scores on the BPRS did not change significantly with either combination of drugs.

Topics: Adult; Antipsychotic Agents; Biperiden; Dibenzocycloheptenes; Dibenzothiepins; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Male; Middle Aged; Piperidines; Pyrrolidines; Schizophrenia; Schizophrenic Psychology

The results of a one year treatment with Melperone are reported. 18 mentally retarded female patients with severe aggressive and autoaggressive behaviour had been included in this open study. Six patients suffered from various epileptic seizures. A significant reduction of aggressive and autoaggressive behaviour, measured by the AFGB, was found. The activity of alkaline phosphatase showed a significant tendency towards normalisation. EEG-controls of patients with epileptic seizures showed no increase of epileptic activity in the EEG. No severe side effects were noticed.

Topics: Adolescent; Adult; Aggression; Alkaline Phosphatase; Antipsychotic Agents; Butyrophenones; Electroencephalography; Epilepsy; Female; Humans; Intellectual Disability; Leukocytes; Piperidines

Topics: Antipsychotic Agents; Fecal Incontinence; Humans; Intellectual Disability; Middle Aged; Phenothiazines; Piperidines; Schizophrenia; Urinary Incontinence

Topics: Antipsychotic Agents; Brain Diseases; Brain Injuries; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Hyperkinesis; Intellectual Disability; Male; Mental Disorders; Phenothiazines; Piperidines; Schizophrenia, Childhood

Topics: Adolescent; Brain Injuries; Child; Diseases in Twins; Humans; Intellectual Disability; Male; Nitriles; Phenothiazines; Piperidines; Psychomotor Disorders; Tranquilizing Agents; Vascular Diseases; Vomiting

Topics: Adolescent; Child; Female; Humans; Intellectual Disability; Male; Nitriles; Personality Disorders; Phenothiazines; Piperidines; Tranquilizing Agents

Topics: Adolescent; Adult; Child; Child Behavior Disorders; Humans; Intellectual Disability; Nitriles; Phenothiazines; Piperidines; Tranquilizing Agents

Topics: Anticonvulsants; Child; Child, Preschool; Female; Humans; Intellectual Disability; Male; Muscles; Piperidines; Propiophenones

Topics: Adolescent; Adult; Aged; Female; Humans; Intellectual Disability; Middle Aged; Nitriles; Phenothiazines; Piperidines; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

Topics: Cerebral Palsy; Child; Child, Preschool; Chlorpromazine; Epilepsy; Epilepsy, Absence; Glutamates; Humans; Infant; Infant, Newborn; Intellectual Disability; Muscles; Piperidines; Pyridoxine; Reserpine; RNA; Spasms, Infantile

Topics: Bipolar Disorder; Butyrophenones; Hallucinations; Humans; Hypnotics and Sedatives; Intellectual Disability; Mental Disorders; Paranoid Disorders; Paresis; Parkinsonian Disorders; Piperidines; Psychomotor Agitation; Psychotic Disorders; Schizophrenia

Topics: Child; Diet, Reducing; Humans; Intellectual Disability; Methylphenidate; Piperidines

Topics: Humans; Intellectual Disability; Piperidines; Schizophrenia

Topics: Diet, Reducing; Intellectual Disability; Piperidines

Topics: Antihypertensive Agents; Diet, Reducing; Epilepsy; Intellectual Disability; Methylphenidate; Muscle Spasticity; Piperidines; Reserpine; Secologanin Tryptamine Alkaloids; Spasm