The Nervous System. Central Nervous System Drugs by Walter S. Root and Frederick G. Hofmann (Eds.)
By Walter S. Root and Frederick G. Hofmann (Eds.)
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It is an effective antagonist of pentylenetetrazol seizures. Another striking example of differences of spectrum of action of these congeners induced by rather small changes in structure can be found in mebutamate, a compound differing from meprobamate only by the replacement of the n-propyl side chain by sec-butyl. Mebutamate, in addition to producing muscle relaxation, paralysis, and sleep, in high doses, appears to have a marked central hypotensive action (43). Stereochemical configuration does not appear to influence paralyzing activity in this large group of compounds as judged by one study of the levo and racemic forms of glyceryl guaiacolate (p.
In fact, moderately enhanced arousal responses to reticular formation stimulation with no decrease in threshold have been observed following the administration of phenaglycodol or meprobamate (153). Evidence for possible higher depressant effects combined with concomitant stimulant effects on the reticular formation by phenaglycodol and particularly by meprobamate is summarized by Killam ( 246 ). Strychnine toxicity is decreased by a 24-hour prior administration of phenaglycodol or thiopental. On the other hand, similar pretreatment results in a significant increase in the toxicity of octamethylpyrophosphoramide (OMPA) (242).
It also blocks the inhibition of the patellar reflex induced by stimulation of the reticular formation, cortex, caudate nucleus, and anterior lobe of the cerebellum. However, the reticular formation inhibition of the knee jerk appears to be less sensitive than facilitation (250). The wide differences in the effects of mephenesin reported (Table II) relate at least in part to differences in preparations, site of electrode placement, and stimulus parameters. In addition to above-discussed actions, the movement elicited by stimulation of cortex, reticular formation, or descending medullary tract is also depressed by mephenesin as are the potentials recorded from the pyramids following strychnine application to the cortex.