benzofurans and Muscle-Rigidity

To explore the therapeutic potential of imidazoline I(1) receptor ligands in motor dysfunction related to the basal ganglia, rigidity was induced in mice by intraperitoneal administration of reserpine. The imidazoline I(1) receptor agonists moxonidine and tizanidine reduced rigidity in a dose-dependent manner. Although rigidity was reduced by efaroxan (an imidazoline I(1) receptor and alpha(2)-adrenoceptor antagonist) and idazoxan (an imidazoline I(1) and I(2) receptor and alpha(2)-adrenoceptor antagonist), SKF86466 and yohimbine, both of which are alpha(2)-adrenoceptor antagonists with no affinity for imidazoline receptors, also suppressed rigidity, suggesting that activation rather than blockade of imidazoline I(1) receptors contributes to reduction of reserpine-induced muscle rigidity.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Antiparkinson Agents; Benzazepines; Benzofurans; Clonidine; Disease Models, Animal; Dose-Response Relationship, Drug; Electromyography; Idazoxan; Imidazoles; Imidazoline Receptors; Injections, Intraperitoneal; Ligands; Male; Mice; Muscle Rigidity; Muscle, Skeletal; Parkinsonian Disorders; Reserpine; Time Factors; Yohimbine

Effects of KW-6629 (7-chloro-N,N,3-trimethylbenzo[b]furan-2-carboxamide) were studied with special reference to the effect on motor and central nervous systems using rats. The drug effectively reduced the motor coordination (rotarod), the anemic decerebrate rigidity, the crossed extensor reflex, and the gamma-activity indirectly recorded from muscle afferent discharges without showing the direct inhibitory effect on muscle spindles. KW-6629 depressed the polysynaptic and dorsal root reflexes without showing marked effect on the monosynaptic reflex in intact spinal cord rats. KW-6629 produced high-amplitude slow wave in the cerebral cortex in electroencephalogram (EEG). KW-6629 did not reduce the EEG after-discharges and behavioral convulsion (amygdaloid kindling). KW-6629 had no effect on the neuromuscular junction. These results suggest that KW-6629 is a centrally acting muscle relaxant which has a site of action in supraspinal structures.

Topics: Animals; Benzofurans; Central Nervous System; Decerebrate State; Electroencephalography; Kindling, Neurologic; Male; Membrane Potentials; Motor Activity; Motor Neurons; Muscle Relaxants, Central; Muscle Rigidity; Neuromuscular Junction; Neurons, Afferent; Rats; Rats, Inbred Strains; Reflex