Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
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Nomifensine and three selected compounds from the series of H4a,H5-trans,H4a,H9b-cis-2,3,4,4a,5,9b-hexahydro-1H-in deno[1,2-b]pyridines have been resolved into their enantiomers. All compounds exhibit pronounced enantioselective activity with respect to their inhibition of tetrabenazine-induced ptosis and potentiation of yohimbine toxicity. Nomifensine exhibits the same preference for one enantiomer with respect to dopamine and norepinephrine reuptake, whereas in the indeno[1,2-b]pyridine series in vitro experiments do not discriminate between the optical antipodes. The absolute stereochemistry of the pharmacologically active enantiomers in both series was determined by X-ray analyses and comparative CD spectra. For biological activity the diphenylmethane is an essential structure feature in both series. Its absolute configuration proved to be 4S for nomifensine and 5S for indenopyridines. The similar pharmacological profile of the two chemical entities is therefore reflected in an identical configuration of this pharmacologically important molecular part.
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PMID:Resolution, absolute stereochemistry, and enantioselective activity of nomifensine and hexahydro-1H-indeno[1,2-b]pyridines. 357 69

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.
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PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61

N-Methyl-D-aspartate (NMDA) antagonists have been demonstrated to suppress the signs of opiate withdrawal; however, side effects limit their clinical use. Since the metabotropic glutamate (mGlu) 5 receptor has been shown to affect glutamate release and modulate NMDA receptor function, we examined the effects of two selective mGlu5 receptor antagonists, 2-methyl-6-(phenyl-ethynyl)-pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), on morphine withdrawal. Pretreatment with MPEP or MTEP (1, 3, and 10 mg/kg, i.p.) significantly attenuated behavioral signs of morphine withdrawal. Specifically, both MPEP and MTEP attenuated the occurrence/severity of chews, digging, salivation, and weight loss, and increased the occurrence of erections. Neither compound changed the occurrence of wet-dog shakes, ptosis, irritability, or lacrimation. Both MPEP and MTEP produced a modest, but significant, attenuation of morphine-withdrawal-induced activation of locus coeruleus neurons in anesthetized rats. These results indicate a role for mGlu5 receptors in morphine withdrawal and suggest the potential for mGlu5 antagonists in the treatment of withdrawal from opiates and other drugs of abuse.
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PMID:The mGlu5 receptor antagonists MPEP and MTEP attenuate behavioral signs of morphine withdrawal and morphine-withdrawal-induced activation of locus coeruleus neurons in rats. 1569 56