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1.
Proc Biol Sci ; 287(1941): 20201798, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33352078

RESUMO

Primary productivity of marine ecosystems is largely driven by broad gradients in environmental and ecological properties. By contrast, secondary productivity tends to be more variable, influenced by bottom-up (resource-driven) and top-down (predatory) processes, other environmental drivers, and mediation by the physical structure of habitats. Here, we use a continental-scale dataset on small mobile invertebrates (epifauna), common on surfaces in all marine ecosystems, to test influences of potential drivers of temperature-standardized secondary production across a large biogeographic range. We found epifaunal production to be remarkably consistent along a temperate to tropical Australian latitudinal gradient of 28.6°, spanning kelp forests to coral reefs (approx. 3500 km). Using a model selection procedure, epifaunal production was primarily related to biogenic habitat group, which explained up to 45% of total variability. Production was otherwise invariant to predictors capturing primary productivity, the local biomass of fishes (proxy for predation pressure), and environmental, geographical, and human impacts. Highly predictable levels of epifaunal productivity associated with distinct habitat groups across continental scales should allow accurate modelling of the contributions of these ubiquitous invertebrates to coastal food webs, thus improving understanding of likely changes to food web structure with ocean warming and other anthropogenic impacts on marine ecosystems.


Assuntos
Recifes de Corais , Invertebrados/fisiologia , Animais , Austrália , Biomassa , Ecossistema , Peixes , Cadeia Alimentar , Humanos , Kelp , Oceanos e Mares , Comportamento Predatório , Temperatura
2.
Adv Mar Biol ; 87(1): 223-258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293012

RESUMO

Outbreaks of the coral eating crown-of-thorns starfish (COTS; Acanthasts cf. solaris) occur in cyclical waves along the Great Barrier Reef (GBR), contributing significantly to the decline in hard coral cover over the past 30 years. One main difficulty faced by scientists and managers alike, is understanding the relative importance of contributing factors to COTS outbreaks such as increased nutrients and water quality, larval connectivity, fishing pressure, and abiotic conditions. We analysed COTS abundances from the most recent outbreak (2010-2018) using both boosted regression trees and generalised additive models to identify key predictors of COTS outbreaks. We used this approach to predict the suitability of each reef on the GBR for COTS outbreaks at three different levels: (1) reefs with COTS present intermittently (Presence); (2) reefs with COTS widespread and present in most samples and (Prevalence) (3) reefs experiencing outbreak levels of COTS (Outbreak). We also compared the utility of two auto-covariates accounting for spatial autocorrelation among observations, built using weighted inverse distance and weighted larval connectivity to reefs supporting COTS populations, respectively. Boosted regression trees (BRT) and generalised additive mixed models (GAMM) were combined in an ensemble model to reduce the effect of model uncertainty on predictions of COTS presence, prevalence and outbreaks. Our results from best performing models indicate that temperature (Degree Heating Week exposure: relative importance=13.1%) and flood plume exposure (13.0%) are the best predictors of COTS presence, variability in chlorophyll concentration (12.6%) and flood plume exposure (8.2%) best predicted COTS prevalence and larval connectivity potential (22.7%) and minimum sea surface temperature (8.0%) are the best predictors of COTS outbreaks. Whether the reef was open or closed to fishing, however, had no significant effect on either COTS presence, prevalence or outbreaks in BRT results (<0.5%). We identified major hotspots of COTS activity primarily on the mid shelf central GBR and on the southern Swains reefs. This study provides the first empirical comparison of the major hypotheses of COTS outbreaks and the first validated predictions of COTS outbreak potential at the GBR scale incorporating connectivity, nutrients, biophysical and spatial variables, providing a useful aid to management of this pest species on the GBR.


Assuntos
Antozoários , Recifes de Corais , Estrelas-do-Mar , Animais , Surtos de Doenças , Larva , Qualidade da Água
3.
Adv Mar Biol ; 87(1): 259-290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293013

RESUMO

Outbreaks of the Pacific crown-of-thorns starfish (COTS; Acanthaster cf. solaris) have been responsible for 40% of the decline in coral cover on the GBR over the last 35 years. With the intensity and frequency of bleaching and cyclonic disturbances increasing, effectively managing these outbreaks may allow reefs an opportunity to recover from these cumulative impacts. Significant research effort has been directed toward developing regional scale models for COTS outbreaks, but these have yet to be fit explicitly to long term time series at the scale of the entire GBR, nor do previous research efforts incorporate explicit estimates of cumulative disturbance history. We developed a stage-based metapopulation model for COTS at a 1×1km resolution using long-term time series and modelled estimates of COTS larval connectivity, nutrient concentrations and important vital rates estimated from the literature. We coupled this metapopulation model to an existing spatially explicit model of coral cover growth, disturbance and recovery across the GBR from 1996 to 2017 to create a metacommunity model. Our results were validated against a spatially and temporally extensive dataset of COTS and coral cover across the GBR, predicting an average coral decline of 1.3% p.a. across the GBR, and accurately recreating coral cover trajectories (mean prediction error=7.1%) and COTS outbreak classification (accuracy=80%). Sensitivity analyses revealed that overall model accuracy was most sensitive to larval predation (boosted regression tree; relative importance=46.7%) and two parameters defining juvenile density dependent mortality (21.5% and 17.5%). The COTS model underestimated peak COTS densities particularly in the Swains and Townsville sectors of the reef, while overestimating COTS density during non-outbreak years. A better understanding of inter-annual variability in larval connectivity, and regionally variable density dependence for adult COTS life stages may improve model fit during these extreme outbreak events. Our model provides a platform to develop upon, and with improvements to estimates of larval connectivity and larval predation could be used to simulate the effects of implementing varying combinations of COTS interventions. This research highlights the importance of the early life history stages of COTS as drivers of outbreak dynamics, emphasizing the need for further empirical research to estimate these parameters.


Assuntos
Antozoários , Recifes de Corais , Estrelas-do-Mar , Animais , Comportamento Predatório
4.
Ecol Appl ; 30(6): e02122, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32159898

RESUMO

Effective environmental management hinges on efficient and targeted monitoring, which in turn should adapt to increasing disturbance regimes that now characterize most ecosystems. Habitats and biodiversity of Australia's Great Barrier Reef (GBR), the world's largest coral reef ecosystem, are in declining condition, prompting a review of the effectiveness of existing coral monitoring programs. Applying a regional model of coral cover (i.e., the most widely used proxy for coral reef condition globally) within major benthic communities, we assess the representation and complementarity of existing long-term coral reef monitoring programs on the GBR. We show that existing monitoring has captured up to 45% of the environmental diversity on the GBR, while some geographic areas (including major hotspots of cyclone activity over the last 30 yr) have remained unmonitored. Further, we identified complementary groups of reefs characterized by similar benthic community composition and similar coral cover trajectories since 1996. The mosaic of their distribution across the GBR reflects spatial variation in the cumulative impact of multiple acute disturbances, as well as spatial gradients in coral recovery potential. Representation and complementarity, in combination with other performance assessment criteria, can inform the cost-effective design and stratification of future surveys. Based on these results, we formulate recommendations to assist with the design of future long-term coral reef monitoring programs.


Assuntos
Antozoários , Tempestades Ciclônicas , Animais , Biodiversidade , Recifes de Corais , Ecossistema
5.
Nat Commun ; 7: 10491, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26839155

RESUMO

Coral reefs are among the most species-rich and threatened ecosystems on Earth, yet the extent to which human stressors determine species occurrences, compared with biogeography or environmental conditions, remains largely unknown. With ever-increasing human-mediated disturbances on these ecosystems, an important question is not only how many species can inhabit local communities, but also which biological traits determine species that can persist (or not) above particular disturbance thresholds. Here we show that human pressure and seasonal climate variability are disproportionately and negatively associated with the occurrence of large-bodied and geographically small-ranging fishes within local coral reef communities. These species are 67% less likely to occur where human impact and temperature seasonality exceed critical thresholds, such as in the marine biodiversity hotspot: the Coral Triangle. Our results identify the most sensitive species and critical thresholds of human and climatic stressors, providing opportunity for targeted conservation intervention to prevent local extinctions.


Assuntos
Biodiversidade , Clima , Conservação dos Recursos Naturais , Recifes de Corais , Ecossistema , Peixes , Estações do Ano , Animais , Tamanho Corporal , Humanos , Estresse Fisiológico , Temperatura
6.
Proc Biol Sci ; 281(1777): 20131993, 2014 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-24403321

RESUMO

The 'diversity-stability hypothesis', in which higher species diversity within biological communities buffers the risk of ecological collapse, is now generally accepted. However, empirical evidence for a relationship between ß-diversity (spatial turnover in community structure) and temporal stability in community structure remains equivocal, despite important implications for theoretical ecology and conservation biology. Here, we report strong ß-diversity-stability relationships across a broad sample of fish taxa on Australia's Great Barrier Reef. These relationships were robust to random sampling error and spatial and environmental factors, such as latitude, reef size and isolation. While ß-diversity was positively associated with temporal stability at the community level, the relationship was negative for some taxa, for example surgeonfishes (Acanthuridae), one of the most abundant reef fish families. This demonstrates that the ß-diversity-stability relationship should not be indiscriminately assumed for all taxa, but that a species' risk of extirpation in response to disturbance is likely to be taxon specific and trait based. By combining predictions of spatial and temporal turnover across the study area with observations in marine-protected areas, we conclude that protection alone does not necessarily confer temporal stability and that taxon-specific considerations will improve the outcome of conservation efforts.


Assuntos
Biodiversidade , Recifes de Corais , Peixes/fisiologia , Animais , Austrália , Biota
7.
J Fish Biol ; 82(2): 367-89, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23398057

RESUMO

Ten years have passed since the last synopsis of whale shark Rhincodon typus biogeography. While a recent review of the species' biology and ecology summarized the vast data collected since then, it is clear that information on population geographic connectivity, migration and demography of R. typus is still limited and scattered. Understanding R. typus migratory behaviour is central to its conservation management considering the genetic evidence suggesting local aggregations are connected at the generational scale over entire ocean basins. By collating available data on sightings, tracked movements and distribution information, this review provides evidence for the hypothesis of broad-scale connectivity among populations, and generates a model describing how the world's R. typus are part of a single, global meta-population. Rhincodon typus occurrence timings and distribution patterns make possible a connection between several aggregation sites in the Indian Ocean. The present conceptual model and validating data lend support to the hypothesis that R. typus are able to move among the three largest ocean basins with a minimum total travelling time of around 2-4 years. The model provides a worldwide perspective of possible R. typus migration routes, and suggests a modified focus for additional research to test its predictions. The framework can be used to trim the hypotheses for R. typus movements and aggregation timings, thereby isolating possible mating and breeding areas that are currently unknown. This will assist endeavours to predict the longer-term response of the species to ocean warming and changing patterns of human-induced mortality.


Assuntos
Ecossistema , Tubarões/fisiologia , Migração Animal , Animais , Conservação dos Recursos Naturais , Demografia , Modelos Biológicos
8.
J Clin Forensic Med ; 12(6): 305-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16188480

RESUMO

A total of 115 suicide cases dealt with by St. Pancras Coroner's Court, London, UK were studied in order to determine what patterns exist regarding the age and gender of the victims and chosen method of suicide. The results were compared with those of a 1998 study of suicides in England and Wales commissioned by the UK Home Office. It was found that suicides in the male population are approximately twice as common as female victims of suicide. In terms of gross number of cases, the peak age group for both males and females resorting to suicide was found to be the 15-44 age group. When the results were standardised according to 2001 census data, however, the most vulnerable age group per head of population for both sexes was 75 and over. Good agreement was found between the results of this study and those of the Home Office Study.


Assuntos
Suicídio/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Asfixia/mortalidade , Afogamento/mortalidade , Feminino , Medicina Legal , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Lesões do Pescoço/mortalidade , Intoxicação/mortalidade , Distribuição por Sexo , Reino Unido/epidemiologia , Ferimentos Penetrantes/mortalidade
9.
J Neurochem ; 59(4): 1302-8, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1402882

RESUMO

The inhibition of high-affinity choline transport by hemicholinium mustard (HCM), an alkylating analogue of hemicholinium-3, was examined in rat brain synaptosomes and guinea pig myenteric plexus. In synaptosomes, 50% high-affinity choline transport inhibition occurs with an HCM concentration of 104 nM (4-min incubation). A 10-min preincubation with 10 microM HCM results in essentially complete (greater than 95%) inactivation that persists after washing. Low-affinity choline transport in synaptosomes is unaffected by HCM inhibition at all concentrations examined (1-50 microM). Time course experiments indicate that the maximum irreversible inhibition (58%) seen after a 1-min preincubation with 500 nM HCM decreases to 46% inhibition after a 15-min preincubation; however, analysis of variance reveals that this difference is not significant. HCM inhibition of acetylcholine release from myenteric plexus-longitudinal muscle preparations persists for at least 2 h after removal of drug from the incubation bath; this inactivation can be prevented by coincubation with a high choline concentration during treatment with the mustard. In contrast, inhibition produced by the parent compound hemicholinium-3 is largely reversed by washing in both preparations examined. The observed potency and selectivity of HCM suggest its usefulness as a covalent probe for high-affinity choline transport.


Assuntos
Colina/antagonistas & inibidores , Hemicolínio 3/análogos & derivados , Acetilcolina/antagonistas & inibidores , Animais , Transporte Biológico/efeitos dos fármacos , Encéfalo/metabolismo , Colina/metabolismo , Cobaias , Técnicas In Vitro , Masculino , Plexo Mientérico/metabolismo , Ratos , Ratos Sprague-Dawley , Sinaptossomos/metabolismo
10.
Mol Pharmacol ; 39(6): 780-7, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1828859

RESUMO

Although many different types of compounds have been tested for 5-hydroxytryptamine1A (5-HT1A) binding affinity, much remains to be learned about the structural requirements associated with 5-HT1A agonism, partial agonism, and antagonism. The present study uses the forskolin-stimulated adenylate cyclase (FSC) assay as a functional screen in rat hippocampal membranes to examine structure-activity relationships for a series of enantiomers of novel analogs of the prototypic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The findings illustrate that there can be large enantiomeric differences in intrinsic activity at the 5-HT1A receptor, independent of enantiomeric effects on binding affinity. Generally, for each enantiomeric pair exhibiting stereoselective 5-HT1A binding, the enantiomer with the higher affinity also displayed the greater amount of 5-HT1A intrinsic activity in the FSC assay. Interestingly, the enantiomers of 8-OH-DPAT itself displayed stereoselective differences in intrinsic activity but not 5-HT1A affinity. Several of the compounds, namely (S)-UH-301, (2R,3R)-CM-12, and (1S,2R)-LEA-146, may have potential as prototypes for selective 5-HT1A antagonists, and (S)-UH-301 itself may be useful as a selective 5-HT1A antagonist. The FSC data presented here are in good agreement with reported measures of in vivo 5-HT1A activity, which were in part the basis of a recently proposed model for the 5-HT1A pharmacophore [J. Med. Chem. 34: 497-510 (1991)].


Assuntos
Adenilil Ciclases/análise , Receptores de Serotonina/metabolismo , Tetra-Hidronaftalenos/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina , Animais , Colforsina/farmacologia , Masculino , Ratos , Ratos Endogâmicos , Estereoisomerismo , Relação Estrutura-Atividade
11.
J Med Chem ; 34(2): 497-510, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1995871

RESUMO

The enantiomers of cis- and trans-1,2,3,4,4a,5,10,10a-octahydro-9-hydroxy-1- propylbenzo[g]quinolines (10 and 11, respectively) and the enantiomers of trans-1,2,3,4,4a,5,6,10b-octahydro-10- hydroxy-4-propylbenzo[f]quinoline (12) have been synthesized and their stereochemical and conformational characteristics have been studied by use of X-ray crystallography and molecular mechanics (MMP2) calculations. The compounds, which are conformationally restricted analogues of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2- (dipropylamino)tetralin (8-OH-DPAT; 1) have been evaluated for central 5-HT and dopamine receptor stimulating activity by use of biochemical and behavioral tests in rats. In addition, we have evaluated the ability of these compounds and a number of previously reported analogues to displace [3H]-8-OH-DPAT from 5-HT1A-binding sites. The enantiomers of 12 behave as potent 5-HT1A-receptor agonists, whereas the octahydrobenzo[g]quinoline derivatives are much less potent or inactive. In general, the affinities of the compounds correlate well with their agonist potencies. The set of compounds under study is accommodated by a novel computer-graphics-derived model for 5-HT1A-receptor agonism. The model consists of a flexible pharmacophore and a partial receptor-excluded volume.


Assuntos
Receptores de Serotonina/efeitos dos fármacos , Tetra-Hidronaftalenos/síntese química , Animais , Fenômenos Químicos , Química , Masculino , Modelos Moleculares , Ratos , Ratos Endogâmicos , Estereoisomerismo , Relação Estrutura-Atividade , Tetra-Hidronaftalenos/farmacologia , Difração de Raios X
12.
J Med Chem ; 33(1): 281-6, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2296024

RESUMO

4-[(2-Chloroethyl)methylamino]-2-butynyl N-(3-chlorophenyl)carbamate (2) and 4-[(2-bromoethyl)methylamino]-2-butynyl N-(3-chlorophenyl)carbamate (3) were synthesized. Compounds 2 and 3 cyclized at neutral pH to an aziridinium ion (4). The rate constants for the cyclization of 2 and 3 at 37 degrees C were about 0.01 and 0.4 min-1, respectively, as measured by titrimetric analysis and by 1H NMR spectroscopy. The aziridinium ion had 1/4 the potency of McN-A-343 (1) as a ganglionic muscarinic stimulant in the anesthetized, pentolinium-treated rat but showed no muscarinic effects on the isolated guinea pig ileum. It caused alkylation of muscarinic receptors in homogenates of the rat cerebral cortex. An irreversible blockade of central muscarinic receptors was also observed after intravenous administration of 3 to mice. Because of its selectivity, irreversible actions, and ability to pass into the central nervous system, 3 should become a valuable tool in studies of muscarinic receptors.


Assuntos
Alcinos/farmacologia , Carbamatos/farmacologia , Receptores Muscarínicos/fisiologia , Alquilação , Alcinos/síntese química , Animais , Pressão Sanguínea/efeitos dos fármacos , Carbamatos/síntese química , Fenômenos Químicos , Química , Ciclização , Cobaias , Íleo/fisiologia , Cinética , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Contração Muscular/efeitos dos fármacos , Quinuclidinil Benzilato/metabolismo , Ratos , Receptores Muscarínicos/efeitos dos fármacos , Análise de Regressão
13.
J Med Chem ; 32(10): 2311-8, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2795604

RESUMO

The enantiomers of 5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten-8-++ +ylamine (3) have been synthesized and evaluated for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor activity by use of behavioral and biochemical tests in rats. In addition, the ability of the compounds to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The absolute configuration of the enantiomers of 3 was determined indirectly by X-ray diffraction of (+)-(8R,alpha R)-5,6,7,8-tetrahydro-1-methoxy-N-(alpha-phenethyl)-9H- benzocyclohepten-8-ylamine hydrochloride (9.HCl), a resolved synthetic precursor. The stereoselectivity of the interaction of 3 with 5-HT1A receptors was more pronounced than that of 8-hydroxy-2-(dipropylamino)tetralin (1; 8-OH-DPAT); only (R)-3 displayed 5-HT activity. However, (R)-3 was of lower potency than any of the enantiomers of 1. The enantiomer (S)-3, which was found to be inactive as a 5-HT-receptor agonist, appeared to be a weakly potent DA-receptor agonist whereas (R)-3 seemed to be devoid of dopaminergic activity. The conformational preferences of 3 were studied by use of NMR spectroscopy and molecular mechanics calculations. Preferred conformations of (R)-3 are similar in shape to those of the stereoselective 5-HT1A-receptor agonist (2R,3S)-8-hydroxy-3-methyl-2-(dipropylamino)tetralin.


Assuntos
Benzocicloeptenos/síntese química , Encéfalo/metabolismo , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/síntese química , Animais , Benzocicloeptenos/farmacologia , Encéfalo/efeitos dos fármacos , Dopamina/metabolismo , Masculino , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores de Serotonina/metabolismo , Reserpina/farmacologia , Serotonina/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Difração de Raios X
14.
J Med Chem ; 32(7): 1590-3, 1989 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2472484

RESUMO

Some 3- and 4-bromophenyl and dimethylsulfonium analogues of the muscarinic agent [4-[[N-(3-chlorophenyl)-carbamoyl]oxy]-2-butynyl] trimethylammonium chloride (McN-A-343) (1) were synthesized. The new compounds were assayed for effects on arterial blood pressure in the pithed rat (ganglionic muscarinic activity). The dimethylsulfonium salts (13a-d) appeared to be partial agonists in relation to 1. The 4-bromophenyl-substituted trimethylammonium iodide 10d exceeded 1 in potency by 3-fold. The compounds retained the selectivity for ganglionic muscarinic receptors shown by 1 since they had only weak effects on the guinea pig ileum in vitro.


Assuntos
Cloreto de (4-(m-Clorofenilcarbamoiloxi)-2-butinil)trimetilamônio/farmacologia , Compostos de Amônio Quaternário/farmacologia , Cloreto de (4-(m-Clorofenilcarbamoiloxi)-2-butinil)trimetilamônio/síntese química , Animais , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Químicos , Química , Relação Dose-Resposta a Droga , Gânglios Parassimpáticos/efeitos dos fármacos , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Metilação , Músculos/efeitos dos fármacos , Ranidae , Ratos , Ácidos Sulfúricos
16.
J Med Chem ; 31(6): 1130-40, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2967376

RESUMO

A number of stereochemically well defined C3-methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been synthesized, and their stereochemical characteristics have been studies by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations. The compounds were tested for activity at central 5-HT and dopamine (DA) receptors, by use of biochemical and behavioral tests in rats. In addition, the ability of the cis- and trans-8-hydroxy-3-methyl-2-(di-n-propylamino)tetralins (15 and 11) to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The stereoselectivity of the interaction of 11 and 15 with 5-HT receptors was much greater than that of 8-OH-DPAT. Observed rank order of potencies in the 5-HT1A binding assay corresponds to that in the in vivo biochemical assay.


Assuntos
Encéfalo/efeitos dos fármacos , Naftalenos/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Tetra-Hidronaftalenos/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Metilação , Conformação Molecular , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Tetra-Hidronaftalenos/síntese química , Difração de Raios X
17.
Eur J Pharmacol ; 143(1): 55-63, 1987 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-2961582

RESUMO

The effects of the four possible C3-methylated stereoisomers of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) ((-)-CM-11, (+)-CM-11, (-)-CM-12, (+)-CM-12) on brain 5-hydroxytryptamine (5-HT) receptor functions were studied in rats. (-)-CM-11 and (+)-CM-12 inhibited dose dependently in all brain parts the accumulation of 5-hydroxytryptophan following decarboxylase inhibition. Their antipodes were inactive. The disappearance of 5-HT induced by alpha-propyldopacetamide was retarded by (-)-CM-11 and (+)-CM-12. The biochemically active isomers produced a flat body posture and forepaw treading. The results indicate that (-)-CM-11 and (+)-CM-12 stimulate 5-HT receptors directly although not as potently as 8-OH-DPAT. The concentration of dopamine was lowered and that of homovanillic acid was elevated by (+)-CM-11 and by both enantiomers of CM-12 in the corpus striatum and in the limbic system of rats. The accumulation of DOPA following decarboxylase inhibition was not markedly changed by any of the compounds. Locomotor activity was enhanced by (+)-CM-11 but not by any of the other compounds, and the effect was haloperidol-resistant. (+)-CM-11 induced no asymmetry in rats in which the corpus striatum was inactivated on one side. Thus, none of the isomers of CM-11 or CM-12 appears to have any effect on the dopamine receptors.


Assuntos
Naftalenos/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Tetra-Hidronaftalenos/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina , Animais , Comportamento Animal/efeitos dos fármacos , Di-Hidroxifenilalanina/metabolismo , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos , Serotonina/metabolismo , Estereoisomerismo , Triptofano Hidroxilase/metabolismo
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