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Figure 1

Figure 1

Mean percentage inhibition of specific radioligand binding by AZD-3043 (50 M). Abbreviations: GABAA = -aminobutyricacidA, BGTX =  bungarotoxin, AMPA = (RS)--amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid, BZD = benzodiazepine, NMDA = N-methyl-D-aspartate, non-sel. = non-selective, PCP = phencyclidine, -R = -resistant, -S = -sensitive, strych. = strychnine.


Figure 1

Figure 2

Mean percentage inhibition of specific radioligand binding by THRX-108893 (200 M), the carboxylate metabolite of AZD-3043. Abbreviations: GABAA = -aminobutyricacidA, BGTX = bungarotoxin, AMPA = (RS)--amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid, BZD = benzodiazepine, NMDA = N-methyl-D-aspartate, non-sel. = non-selective, PCP = phencyclidine, -R = -resistant, -S = -sensitive, strych. = strychnine.


Figure 1

Figure 3

VEHICLE

1.0

0

-1.0

Representative effect of bolus IV administration of vehicle (1 mL/kg) on rat electroencephalographic activity. Administration of vehicle coincides with the vertical line on the tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). The vehicle did not produce a suppression of electroencephalographic activity.


Figure 1

Figure 4

AZD-3043 (5 mg/kg)

1.0

0

-1.0

Representative effect of bolus IV administration of AZD-3043, 5 mg/kg, on rat electroencephalographic activity. Administration of AZD-3043 coincides with the vertical line on the tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). AZD-3043 produced a suppression of electroencephalographic activity.


Figure 1

Figure 5

AZD-3043 (10 mg/kg)

1.0

0

-1.0

Representative effect of bolus IV administration of AZD-3043, 10 mg/kg, on rat electroencephalographic activity. Administration of AZD-3043 coincides with the vertical line on the tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). AZD-3043 produced a suppression of electroencephalographic activity.


Figure 1

Figure 6

AZD-3043 (20 mg/kg)

1.0

0

-1.0

Representative effect of bolus IV administration of AZD-3043, 20 mg/kg, on rat electroencephalographic activity. Administration of AZD-3043 coincides with the vertical line on the tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). AZD-3043 produced a suppression of electroencephalographic activity.


Figure 1

Figure 7

AZD-3043 (30 mg/kg)

1.0

0

-1.0

Representative effect of bolus IV administration of AZD-3043, 30 mg/kg, on rat electroencephalographic activity. Administration of AZD-3043 coincides with the vertical line on the tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). AZD-3043 produced a suppression of electroencephalographic activity.


Figure 1

Figure 8

Vehicle

1.0

0

-1.0

Representative effect (following 1 week washout) of bolus IV administration of vehicle, 1 mL/kg, on rat electroencephalographic activity. Administration of vehicle coincides with the vertical line on each tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). The vehicle did not produce a suppression of electroencephalographic activity.


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Figure 9

Propofol (1 mg/kg)

1.0

0

-1.0

Representative effect (following 1 week washout) of bolus IV administration of propofol, 1 mg/kg, on rat electroencephalographic activity. Administration of propofol coincides with the vertical line on each tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). Propofol produced a suppression of electroencephalographic activity.


Figure 1

Figure 10

Propofol (3 mg/kg)

1.0

0

-1.0

Representative effect (following 1 week washout) of bolus IV administration of propofol, 3 mg/kg, on rat electroencephalographic activity. Administration of propofol coincides with the vertical line on each tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). Propofol produced a suppression of electroencephalographic activity.


Figure 1

Figure 11

Propofol (6 mg/kg)

1.0

0

-1.0

Representative effect (following 1 week washout) of bolus IV administration of propofol, 6 mg/kg, on rat electroencephalographic activity. Administration of propofol coincides with the vertical line on each tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). Propofol produced a suppression of electroencephalographic activity.


Figure 1

Figure 12

Propofol (10 mg/kg)

1.0

0

-1.0

Representative effect (following 1 week washout) of bolus IV administration of propofol, 10 mg/kg, on rat electroencephalographic activity. Administration of propofol coincides with the vertical line on each tracing. Data points represent 2-second epochs of processed electroencephalographic activity. The activation state is expressed on the ordinate (1.0 at the top = fully activated state, -1.0 at the bottom = fully inactivated state). Propofol produced a suppression of electroencephalographic activity.


Figure 1

Figure 13

Before AZD-3043

Representative electroencephalography recordings in rats prior to hypnosis with AZD-3043 (20 mg/kg).


Figure 1

Figure 14

Before Propofol

Representative electroencephalography recordings in rats prior to hypnosis with propofol (6 mg/kg).


Figure 1

Figure 15

AZD-3043 (20 mg/kg)

Representative electroencephalography recordings in rats during hypnosis with AZD-3043 (20 mg/kg).


Figure 1

Figure 16

Propofol (6 mg/kg)

Representative electroencephalography recordings in rats during hypnosis with propofol (6 mg/kg).


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