Treatment of Parkinson's disease with L-dopa therapy leads to long-term complications, including loss of drug efficacy and the onset of dyskinesia. Adenosine A2A receptors in striatum are selectively localized to GABAergic output neurons of the striato-pallidal pathway and may avoid such problems. The novel adenosine A2A receptor antagonist KW-6002 has been examined for antiparkinsonian activity in MPTP-treated primates. Oral administration of KW-6002 reversed motor disability in MPTP-treated common marmosets in a dose-dependent manner. However, KW-6002 only modestly increased overall locomotor activity and did not cause abnormal movement, such as stereotypy. The ability of KW-6002 to reverse motor disability was maintained on repeated daily administration for 21 days, and no tolerance was observed. KW-6002 induced little or no dyskinesia in MPTP-treated primates previously primed to exhibit dyskinesia by prior exposure to L-dopa. These results suggest that selective adenosine A2A receptor antagonists represent a new class of antiparkinsonian agents that improve disability without producing hyperactivity and without inducing dyskinesia.

OBJECTIVE: Con¯icting results have emerged over the nature of autonomic nervous system abnormalities in human obesity. This present study was designed to investigate the sympatho-vagal activities and their responsiveness to acute cold exposure in age-and height-matched obese and non-obese young women. SUBJECTS: Twenty-four age-and height-matched obese (Weight: 68.1 AE 2.64 kg, BMI: 26.3 AE 0.74 kgam 2 , %Fat: 39.9 AE 1.23%) and non-obese young women (Weight: 46.9 AE 0.77 kg, BMI: 18.5 AE 0.18 kgam 2 , %Fat: 22.9 AE 0.8%). MEASUREMENTS: Plasma leptin, insulin, glucose and lipid concentrations were measured at rest. The sympathetic (SNS) and parasympathetic (PNS) nervous system activities were assessed by means of power spectral analysis of heart rate variability (HRV) for 15 min under control (25 C) or acute cold exposure (10 C) conditions. The very low (VLO) frequency component, and SNS (lowahigh power), and PNS (highatotal power) indexes were used to evaluate thermoregulatory sympathetic function, and cardiac sympathetic and parasympathetic nervous activities, respectively. RESULTS: Plasma leptin concentration was signi®cantly greater in the obese than in the control group (47.3 AE 7.00 vs 12.1 AE 1.22 ng Á ml 71 , P`0.001). There was a highly positive correlation between plasma leptin concentration and percent of body fat (r 0.863, P`0.001). During the resting condition, there was no signi®cant difference in any of the parameters of the HRV between the obese and control groups. Upon acute cold exposure, the VLO frequency component associated with thermoregulation (309 AE 49.9 vs 578 AE 142.2 ms 2 , P`0.05) as well as its responsiveness (25 ± 10 C delta changes: 17 AE 82.9 vs 326 AE 138.2 ms 2 , P`0.05) were signi®cantly lower in the obese than in the control group. CONCLUSION: Our data indicate that a reduced autonomic, especially sympathetic responsiveness associated with thermoregulation and possibly leptin resistance might be aetiological factors of obesity in young women.

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