Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of N-(4-amino-2-butynyl)-5-methyl-2-pyrrolidones modified only in the amino group was synthesized. The compounds were agonists, partial agonists, and antagonists on the isolated guinea pig ileum. They had greater affinity and lower intrinsic efficacy at ileal muscarinic receptors than the identically modified N-(4-amino-2-butynyl)-2-pyrrolidones and N-(4-amino-2-butynyl)succinimides. Dissociation constants in the three series were correlated, suggesting that the compounds had similar mode of binding to muscarinic receptors. The 5-methyl-2-pyrrolidones were 10- to 20-fold less potent as muscarinic agonists on the guinea pig urinary bladder than on the ileum and also elicited lower relative maximal responses on the bladder. For example, the trimethylammonium (9) and azetidino (10) analogues were equipotent (EC50 = 0.2 microM) with the selective muscarinic stimulant N-(1-methyl-4-pyrrolidino-2-butynyl)-N-methylacetamide, BM 5 (2), as agonists on the ileum, but on the bladder 9 and 10 were relatively weak partial agonists, whereas 2 was an antagonist. Compound 10, like 2 and the dimethylamino analogue 8, also differentiated between centrally mediated muscarinic effects in vivo as it was potent in producing analgesia and hypothermia but did not elicit tremor. Instead, 10 antagonized oxotremorine-induced tremor. Thus, 10 resembled 2 in its actions except that the greater intrinsic efficacy of 10 shifted the balance between agonist and antagonist properties slightly toward agonism. Manipulation of intrinsic efficacy by minor changes in chemical structure is emphasized as a means of attaining selectivity.
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PMID:5-Methyl-2-pyrrolidone analogues of oxotremorine as selective muscarinic agonists. 334 81

Dissociation involves disruptions of usually integrated functions of consciousness, perception, memory, identity, and affect (e.g., depersonalization, derealization, numbing, amnesia, and analgesia). While the precise neurobiological underpinnings of dissociation remain elusive, neuroimaging studies in disorders, characterized by high dissociation (e.g., depersonalization/derealization disorder (DDD), dissociative identity disorder (DID), dissociative subtype of posttraumatic stress disorder (D-PTSD)), have provided valuable insight into brain alterations possibly underlying dissociation. Neuroimaging studies in borderline personality disorder (BPD), investigating links between altered brain function/structure and dissociation, are still relatively rare. In this article, we provide an overview of neurobiological models of dissociation, primarily based on research in DDD, DID, and D-PTSD. Based on this background, we review recent neuroimaging studies on associations between dissociation and altered brain function and structure in BPD. These studies are discussed in the context of earlier findings regarding methodological differences and limitations and concerning possible implications for future research and the clinical setting.
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PMID:Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder. 2813 24