Bioisosteric replacement of the alpha-amino carboxylic acid functionality in 2-amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobutene-1,2-dione containing NMDA antagonists.

In this report, a novel bioisostere of the alpha-amino acid, 3,4-diamino-3-cyclobutene-1,2-dione, has been incorporated into a series of compounds which are NMDA antagonists. These compounds, which are achiral and easily prepared, demonstrated good affinity at the NMDA receptor by their ability to displace [3H]CPP binding in vitro. In particular, the phosphonic acid 24 provided protection against NMDA-induced lethality in mice equivalent to 2-amino-7-phosphonoheptanoic acid (5).

Polyol pathway activity in nervous tissues of diabetic and galactose-fed rats: effect of dietary galactose withdrawal or tolrestat intervention therapy.

Enhanced polyol pathway activity resulting in an accumulation of sorbitol and a depletion of myoinositol in nervous tissues has been proposed to be important in development of diabetic neuropathies. This investigation demonstrated that in two models of diabetic complications, streptozocin (STZ)-induced diabetic rats and galactose-fed rats, 5 weeks of disease led to an accumulation of sorbitol or galactitol, respectively, in three cranial nerves (the optic (II), trigeminal (V), and vagus (X) nerves), as well as the sciatic nerve, cerebral cortex, and retina. In both models, the cranial nerves and cerebral cortex contained lower levels of accumulated polyol than the sciatic nerve.

Cranial nerve dysfunction in conscious galactosemic rats as measured by the auditory-evoked brainstem response.

The purpose of this study was to extend our previous work with the auditory-evoked brainstem response and determine whether galactosemia would produce a functional neuropathy similar to that previously seen in streptozocin-induced diabetic rats. Sprague-Dawley male rats implanted with cortical electrodes received either normal chow (n = 17) or a 50% galactose diet (n = 17) for 5 weeks. Peak II latency of the auditory-evoked brainstem response, interpreted as a functional measure of the auditory nerve (VIII cranial) in rats, was significantly prolonged in galactose-fed rats relative to controls (P less than 0.

Tolrestat, an aldose reductase inhibitor, prevents nerve dysfunction in conscious diabetic rats.

The effect of 4 wk of streptozocin (STZ)-induced diabetes on the transmission time of the auditory-evoked brain stem response (ABR) was examined in conscious male Sprague-Dawley rats. Distal nerve transmission time of the auditory pathway (latency of peak II), which includes conduction along the 8th cranial nerve, increased in diabetic rats (n = 9) relative to nondiabetic rats (n = 17). The difference in peak II latency between diabetic and control rats was significant beginning 2 wk after the induction of diabetes (P less than .

The motor program and role of sensory feedback in claw extension of the crayfish.

The motor program and role of the meropodite sensory organs (the chordotonal organs MC-1, MC-2 and the myochordotonal organ MCO) in extension of the merocarpodite (M-C) joint of the claw was examined during an antennal-evoked defense response. Recordings from the meropodite extensor muscle indicated that the tonic extensor motoneuron was primarily responsible for M-C joint extension. The phasic extensor motoneuron was co-activated with the tonic motoneuron in only 48% of the responses.

Baroreflex control of renal sympathetic nerve activity in hypertensive miniature swine.

The baroreceptor reflex control of renal nerve activity was examined in seven normotensive and 14 deoxycorticosterone acetate-treated anesthetized Yucatan miniature swine. Pressor responses evoked by the administration of phenylephrine were used to assess reflex control. The mean absolute threshold for inhibition of renal nerve activity was higher but not significantly different between the deoxycorticosterone acetate-treated and normotensive group.

Role of the hemigiant neurons in the crayfish defense response.

The medial and lateral hemigiant neurons of the crayfish were isolated in the circumesophageal connective and electrically stimulated to examine their ability to elicit a defense response. In contrast to previous reports, neither a defense response nor any other thoracic or abdominal movements were observed following stimulation of either hemigiant. Small fibers that lie adjacent to the hemigiants in the circumesophageal connective evoked defense responses when they were electrically stimulated.

Anatomical organization of neurons descending from the supraesophageal ganglion of the lobster.

A population of somata in the supraesophageal ganglion of the lobster was filled by retrograde diffusion of cobalt through the circumesophageal connectives. These somata are located predominantly in the dorsal anterior median region of the protocerebrum. They are organized into a contralateral and two ipsilateral clusters.