Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part II: Central and peripheral nervous systems.

Pharmacological properties of midaglizole (DG-5128, CAS 66529-17-7) on central and peripheral nervous systems were investigated in comparison with those of tolbutamide. 1. Central nervous system: Midaglizole showed little or no effects on general behavior (mouse), spontaneous motor activity (mouse), hexobarbital anesthesia (mouse), conditioned avoidance response (rat) and body temperature (rabbit) at an oral dose of 100 mg/kg. It also produced little or no changes in electroencephalogram (cat) and spinal reflex (cat) after intravenous dosing of 10 mg/kg. The drug lacked anticonvulsant and analgesic activities (mouse). Midaglizole produced clonic convulsion, mydriasis, lacrimation, increase in pinna reflex, decrease in spontaneous motor activity, increase in pain threshold (mouse) and rise in body temperature (rabbit) at oral dose of 300 mg/kg. Tolbutamide showed similar effects except that it potentiated hexobarbital anesthesia, slightly decreased convulsion and tended to decrease body temperature. 2. Autonomic nervous system: Midaglizole potentiated the pressor response to norepinephrine and inhibited the depressor response to acetylcholine at an intravenous dose of 10 mg/kg (anesthetized dogs). Similar results were observed after dosing of tolbutamide. Midaglizole potentiated the contractile response of nictitating membrane to pre- and post-ganglionic cervical sympathetic nerve stimulation after intravenous dosing of 1 mg/kg (cat). Tolbutamide lacked the activity on the contraction elicited by both stimulations. Midaglizole and tolbutamide had little or no effect on pupil size (rabbit). 3. Skeletal muscle contraction (neuromuscular junction): Midaglizole (3-10 mg/kg i.v.) slightly potentiated the tibialis anterior muscle contraction induced by peroneal nerve stimulation, but did not potentiate the contraction by direct (muscle) stimulation (rabbit). On the other hand, tolbutamide increased the contraction induced by both nerve and muscle stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)