Marthe Cohn

A direct effect of dibutyryl cycluc AMP on the duration of narcosis induced by sedative, hypnotic, tranquiliser and anaesthetic drugs in the rat ☆

Abstract The ability of exogenously administered N6, O2′-dibutyryl analogue of cyclic AMP to shorten, in a dose-related manner, the duration of narcosis of eight structurally different agents (chloral hydrate, paraldehyde, diazepam, amobarbital, halothane, ketamine, ethanol and methanol) has been demonstrated in the rat. No other nucleotide, neurotransmitter, biogenic amine or hormone tested, shortened, in a dose-related manner the sleeping time induced by the anaesthetic agents.

Epidural morphine and methylprednisolone. New therapy for recurrent low-back pain.

Twenty patients with intractable, postoperative, recurrent low-back pain were treated with a sequential, epidural injection of morphine (8 mg) and methylprednisolone acetate (80 mg). Concomitantly administered, these drugs provided 50-100% pain relief lasting 6-24 months and elicited prolongations of mood elevation and morphine-induced side effects. Evidence from computed tomography and electromyography, however, indicated no amelioration of pre-existing pathologies.

Regulation of behavioral events by thyrotropin releasing factor and cyclic AMP.

Like dibutyryl cyclic AMP, thyrotropin releasing factor (TRF) has potent antianesthetic properties, but only dibutyryl cyclic AMP shortens narcosis dose-relatedly. In contrast, only TRF reverses amobarbital-induced hypothermia (dose-relatedly). In naive rats, dibutyryl cyclic AMP (25-200 mug) induces convulsions while TRF (5-100 mug) produces intermittent hyperactivity and sedation but never convulsions. To determine whether behavioral events may be regulated in the central nervous system through an interaction of the two naturally occurring compounds, TRF (5-100 mug) and dibutyryl cyclic AMP (25-200 mug) were injected simultaneously into the lateral ventricle of the brain of naive rats or rats anesthetized with amobarbital (80 mg/kg). TRF (12.5-50 mug) and dibutyryl cyclic AMP (100-200 MUG) DID NOT SHORTEN NARCOSIS FURTHER THAN DIBUTYRYL CYCLIC AMP alone. Amobarbital protected against the lethal effects of the two compounds injected simultaneously. Long-lasting locomotor disorders and mortality rate increased with increasing doses of TRF (12.5-25 mug) and dibutyryl cyclic AMP (100-200 MUG) GIVEN TO NAIVE RATS. Results did not support the postulate that cyclic AMP is the second messenger of TRF.

Comparisons between the antianesthetic action of dibutyryl cyclic AMP and analeptic drugs on amobarbital-induced narcosis in the rat.

The dose-related antianesthetic and antidotal property of dibutyryl cyclic AMP, devoid of toxic effects, imparts uniqueness to the nucleotide as an arousal agent. Of the analeptic drugs studied (d-amphetamine, picrotoxin, pentylenetetrazol, caffeine, theophylline, strychnine, ethamivan and doxapram), only picrotoxin demonstrated antianesthetic properties. However, picrotoxin was associated with severe toxicity at all dose levels tested. No analeptic drug is effective in reversing the central nervous system depression produced by sedative, hypnotic or tranquilizer drug overdosage.

Measurements of brain amobarbital concentrations in rats anesthetized and overdosed with amobarbital and treated centrally with dibutyryl cyclic AMP

Abstract Three doses of amobarbital, an anesthetic dose (80 mg/kg), a minimum lethal dose (130 mg/kg), and a high lethal dose (180 mg/ kg) were administered intraperitoneally to groups of rats. All rats were injected intracerebroventricularly with 0.9% saline or dibutyryl cyclic AMP, 200 μg/rat. While those rats treated with saline solution were still sleeping at decapitation and those treated with dibutyryl cyclic AMP were awake, there were no significant differences in their brain concentrations of amobarbital.