Figure 3.

Anxiolytic (A), anticonvulsant (B), muscle relaxant (C), and sedative (D) activity of ZK200775 in rodents. For assessment of anxiolytic activity (A) of ZK200775, 0.3, 1.0, and 3.0 mg/kg i.p. (30 min), mice were placed in the center of a chamber with a floor divided into four plates and, after 20 s of exploration, received a shock (1 mA, 60 ms) each time crossing from one plate to another. The number of crossings within 1 min were taken as a measure of exploratory activity. Experimental groups consisted of eight mice. ANOVA showed significant main effect [F(3, 30) = 4.8; P < 0.01] revealing that ZK200775 increased punished locomotor activity in mice. For assessment of the threshold for clonic seizures (B), AMPA, kainate or NMDA (1 nmol/5 μl) were infused continuously intracerebroventricularly to mice with a speed of 5 μl/min. ZK200775 was administered i.v. 5 min before the seizure test. The time in seconds to a clonic seizure was used as an endpoint determining susceptibility to convulsions. The THRD₅₀ (threshold dose) was calculated in nanomols by means of regression analysis. Experimental groups consisted of five to eight mice. *P < 0.05; **P < 0.01; ***P < 0.001 vs. vehicle-treated mice. Muscle relaxant (C) effect of ZK200775 was measured in electromyogram (EMG) recorded from gastrocnemius muscle of genetically spastic rats after i.v. administration of ZK200775 (open circles), 1 (dotted), 3 (dash-dotted), 10 (dashed), and 30 (solid) mg/kg or vehicle (filled circles). The electrical signals were amplified, band-pass filtered (5–10 kHz), full wave rectified, and normalized. The electromyogram was recorded continuously, and the average integrated activity was determined in 5-min intervals over 2 h. Experimental groups consisted of 5–12 rats. ANOVA revealed that ZK200775 decreased muscle tone in genetically spastic rats in a dose- [F_dose(4, 36) = 15.88; P < 0.0001] and time-dependent [F_time(4, 144) = 7.41, P < 0.0001] manner. Exploratory activity (D) in NMRI mice was monitored over 5 min beginning immediately after i.v. administration of ZK200775. Experimental groups consisted of eight mice. ED₅₀ was calculated by means of regression analysis. *P < 0.05; ***P < 0.001 vs. vehicle-treated mice.