Explore the vast range of titles available.

The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study.

N,N -dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N -dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. To further clarify the pharmacology of hallucinogenic tryptamines, we synthesized DMT, N -methyl- N -isopropyltryptamine (MIPT), N,N -dipropyltryptamine (DPT), and N,N -diisopropyltryptamine. We then tested the abilities of these N,N -dialkyltryptamines to inhibit [ 3 H]5-HT uptake via the plasma membrane serotonin transporter (SERT) in human platelets and via the vesicle monoamine transporter (VMAT2) in Sf9 cells expressing the rat VMAT2. The tryptamines were also tested as inhibitors of [ 3 H]paroxetine binding to the SERT and [ 3 H]dihydrotetrabenazine binding to VMAT2. Our results show that DMT, MIPT, DPT, and DIPT inhibit [ 3 H]5-HT transport at the SERT with K I values of 4.00 ± 0.70, 8.88 ± 4.7, 0.594 ± 0.12, and 2.32 ± 0.46 μM, respectively. At VMAT2, the tryptamines inhibited [ 3 H]5-HT transport with K I values of 93 ± 6.8, 20 ± 4.3, 19 ± 2.3, and 19 ± 3.1 μM, respectively. On the other hand, the tryptamines were very poor inhibitors of [ 3 H]paroxetine binding to SERT and of [ 3 H]dihydrotetrabenazine binding to VMAT2, resulting in high binding-to-uptake ratios. High binding-to-uptake ratios support the hypothesis that the tryptamines are transporter substrates, not uptake blockers, at both SERT and VMAT2, and also indicate that there are separate substrate and inhibitor binding sites within these transporters. The transporters may allow the accumulation of tryptamines within neurons to reach relatively high levels for sigma-1 receptor activation and to function as releasable transmitters.

Canberra is a city of orphans. People arrive temporarily for work, but stay on because they discover unanticipated promise and opportunity in a city that the rest of the country loathes but can’t really do without. Daley’s Canberra begins and ends at the lake and its forgotten suburbs, traces of which can still be found on Burley Griffin’s banks. It meanders through the cultural institutions that chronicle the unsavoury early life of Canberra, the graveyard at St John’s where the pioneers rest and the mountains that surround the city. In Canberra people don’t ask you where you went to school, as they do in Melbourne, or where your house is and how much you paid for it, as they do in Sydney. They ask you where you’ve come from. And how long you’re going to stay.

KURNELL IS A no-fuss, unpretentious place given that it's supposed to be the cradle of the nation. Stretching along a promontory that looks like a witch's finger pointing west from the southern shore of Botany Bay, opposite Sydney Airport, Kurnell is a hotchpotch sprawl of fibro modesty and glass-and-steel ambition, where trailered speedboats rest on the verges and Aussie flags snap on front-yard poles.

A BRISK WESTERLY WHIPS Up Salty whitecaps as the ferry rises and plunges, churns and slices, through a lazy emerald swell, upriver towards Parramatta. It's midday on a Monday. Two international tourists in sensible hats with day-packs and selfie-sticks have been agitated since I responded that, 'No, sorry, you're going the wrong way' for the harbour bridge and opera house.

I'VE CHOSEN AUTHORS born in the twentieth century, whose work was published over a span of not quite half a century, from 1941 to the year of the bicentenary, 1988. I know: I've chosen three books published over some 47 years when there's almost another 230 colonial and post- colonial years and, of course, 60,000 more with rich stories of continental habitation to choose from.

JIMMY CLEMENTS, a Wuradjuri man from down Gundagai way, walked all the way up to Canberra on hearing that the Duke and Duchess of York were set to open the new federal parliament.

Canberra, Australia, is a city of orphans. People arrive temporarily for work, but stay when they discover the unanticipated promise and opportunity Canberra has to offer. An exploration of the city Australia loves to hate, this book shows that there is more to this capital than politics, geometrically designed roads, and mid-century architecture. From the lake and its forgotten suburbs—traces of which can still be found on Burley Griffin's banks—to the mountains that surround the city, this account also examines the unsavory early life of Canberra and the graveyard at St John's, where the pioneers rest. 

AROUND POZIÈRES, in northern France, they insisted that the winter before last was the most bitter in four decades. This was fortunate because I was there researching the Collingwood football player Percy Rowe, also known as Paddy Rowan, who died on the Somme in December 1916 during a winter the locals also reckoned was the nastiest for forty years.