Search PubMed⌕ Search

Biomedical subjects

G H Fromm

Publications and source records attributed to G H Fromm.

At least 37 records · Page 2Linked to original sources
PubMed1987

Comparison of L-baclofen and racemic baclofen in trigeminal neuralgia.

L-Baclofen was compared with racemic baclofen (Lioresal) in a double-blind crossover trial in 15 patients with typical trigeminal neuralgia. L-Baclofen was more effective than five times as much racemic baclofen in nine patients. Six of these nine patients have continued pain-free on L-baclofen for 4 to 17 months (mean, 10 months). L-Baclofen was much better tolerated than racemic baclofen. Our results suggest that L-baclofen represents a significant improvement over racemic baclofen in the treatment of trigeminal neuralgia, and support our laboratory observations indicating that D-baclofen antagonizes the action of L-baclofen.

Adult↗
PubMed1986

Role of inhibitory mechanisms in staring spells.

Phenomena of a negative nature--a motionless stare with arrest of mental activity--characterize absence seizures and some complex partial seizures. In agreement with this clinical observation, it has been found that the slow waves of the spike-wave complex are associated with inhibitory postsynaptic potentials and cessation of neuron firing in both humans and experimental animals. Gamma-aminobutyric acid (GABA) concentration is increased in the cerebral cortex in some experimental models of spike-wave discharge, and GABA agonists exacerbate spike-wave discharges in a variety of experimental models. GABAergic neurons and terminals are also increased in the hippocampus of seizure-sensitive gerbils, and kindling of the hippocampus and amygdala appears to enhance GABAergic inhibitory mechanisms. Antiabsence drugs selectively depress inhibitory pathways in the central nervous system, providing further evidence in support of the hypothesis that absences represent inhibitory paroxysms. Antiabsence drugs also appear to be useful adjunctive drugs in the treatment of complex partial seizures associated with spike-wave discharges, suggesting that here too inhibitory mechanisms may play a prominent role. All these clinical, physiological, and pharmacological observations would indicate that staring spells represent inhibitory seizures, occurring primarily in absences and secondarily in some complex partial seizures.

Anticonvulsants↗
PubMed1986

Sinus arrest in epilepsy.

In contrast to the usual occurrence of tachycardia during epileptic seizures, a 23-year-old man had episodic prolonged sinus arrest that lasted up to 9 seconds at the time of clinically observed seizures. There was no demonstrable cardiac disease.

Adult↗
PubMed1985

Baclofen as an analgesic in chronic peripheral nerve disease.

Baclofen has shown analgesic properties in a number of animal studies but has failed as a conventional analgesic in the human postoperative dental pain model. In order to test baclofen's analgesic properties in more chronic pain conditions, we selected postherpetic neuralgia and diabetic neuropathy pain as possible trial diseases for baclofen analgesia. 15 patients with postherpetic neuralgia and 10 with diabetic neuropathy pain were treated with baclofen. In the spinal postherpetic neuralgia group and diabetic neuropathy group, there was little evidence of analgesic effect. 6 of 7 patients with facial postherpetic neuralgia had a good response to baclofen during the 3-week trial. Baclofen does not appear to be a conventional analgesic.

Adult↗
PubMed1985

Effects of different classes of antiepileptic drugs on brain-stem pathways.

Antiepileptic drugs probably act by preventing the spread of the abnormal paroxysmal activity from the epileptogenic focus to surrounding normal neurons. An investigation of the mechanism of action of established anticonvulsant drugs on normal neuronal systems may therefore offer useful insights into the pathogenesis of the seizure disorders that these drugs serve to control. Antiabsence drugs (ethosuximide, valproate) depress reticular inhibitory pathways. Drugs effective against generalized tonic-clonic seizures (phenytoin, carbamazepine, valproate) depress reticular excitatory pathways. Drugs that are also effective against trigeminal neuralgia (phenytoin, carbamazepine) also depress afferent excitation and facilitate segmental inhibition in the trigeminal complex. Drugs that depress afferent excitation and facilitate segmental inhibition but do not depress the reticular system (baclofen) are effective against trigeminal neuralgia but do not have clinical antiepileptic properties. These observations indicate that the ability to depress the reticular core is an important characteristic of antiepileptic drugs, and suggest that the reticular core is involved in the spread and generalization of clinical seizures.

Animals↗
PubMed1984

Differential effect of antiepileptic and non-antiepileptic drugs on the reticular formation.

The effect of the antiepileptic drugs carbamazepine and phenytoin, and of the non-antiepileptic drug baclofen, was compared on various inhibitory and excitatory mechanisms in the feline trigeminal nucleus. Baclofen resembled carbamazepine and phenytoin in depressing segmental excitatory and facilitating segmental inhibitory mechanisms. However, baclofen facilitated the periventricular and periaqueductal inhibition of the trigeminal nucleus, while carbamazepine and phenytoin depressed these descending inhibitory mechanisms. Baclofen also resembles carbamazepine and phenytoin in its effectiveness in trigeminal neuralgia, but baclofen is not a clinically effective antiepileptic agent. Our experiments indicate that the ability to depress the reticular formation of the diencephalon and midbrain is an important characteristic of antiepileptic drugs. This suggests that the reticular core is involved in the spread and generalization of seizures.

Action Potentials↗
PubMed1984

Trigeminal neuralgia. Current concepts regarding etiology and pathogenesis.

There has long been a controversy over the cause of trigeminal neuralgia. Most clinical data favor a peripheral cause. However, most of the experimental data tend to favor a central mechanism. Drugs that are effective in the treatment of trigeminal neuralgia facilitate segmental inhibition in the trigeminal nucleus, as well as depressing excitatory transmission. The most plausible hypothesis to reconcile all of these observations is that trigeminal neuralgia has a peripheral cause and a central pathogenesis. Chronic irritation of the trigeminal nerve apparently leads to both a failure of segmental inhibition in the trigeminal nucleus, and ectopic action potentials in the trigeminal nerve. This combination of increased firing and impaired efficiency of inhibitory mechanisms leads to paroxysmal discharges in the trigeminal nucleus, which are perceived as attacks of trigeminal neuralgia when they involve nociceptive trigeminothalamic-relay neurons.

Baclofen↗
PubMed1984

Baclofen in the treatment of trigeminal neuralgia: double-blind study and long-term follow-up.

A double-blind crossover study of the effects of baclofen was conducted on 10 patients with typical trigeminal neuralgia. Baclofen significantly decreased the number of painful paroxysms in 7 of the 10 patients. An open trial in another 50 patients with trigeminal neuralgia refractory to or unable to tolerate carbamazepine showed that 37 (74%) were relieved of their attacks by baclofen, either alone (12 patients) or in combination with previously ineffective doses of carbamazepine or phenytoin (25). On long-term follow-up of one to five years (mean, 3.0 years), 18 of the 60 patients (30%) continued pain free while receiving baclofen; 10 (17%) went into remission after 3 to 6 months; 13 (22%) became refractory to baclofen after 1 to 18 months; and 2 (3%) elected operation despite a good response to baclofen. The results indicate that baclofen is a useful drug in the treatment of trigeminal neuralgia.

Adult↗
PubMed1983

Baclofen. Its effect on seizure frequency.

Baclofen has been reported to be epileptogenic in man, but many animal studies have demonstrated an anticonvulsant effect. In 12 patients with a history of epilepsy, baclofen was given in the conventional dosage range. In the six patients with anticonvulsant-controlled seizures, none had a seizure during baclofen therapy. In the six patients with uncontrolled epilepsy, two patients had one more seizure per month while receiving baclofen, and a third went from four seizures per month to one per month. Baclofen does not appear to have a deleterious effect in patients with epilepsy.

Adult↗
PubMed1983

Is baclofen an analgesic?

Baclofen has been reported to be an analgesic in a wide variety of animal pain models. To study the analgesic potential of baclofen in humans, we used a postoperative dental pain model. Thirty-three patients were enrolled in a double-blind study using either baclofen, acetaminophen, or placebo. There was a statistically significant difference in pain reduction at 1 and 2 h after acetaminophen ingestion, compared to that of placebo. Baclofen was not statistically superior to placebo at any one of the four hourly measurements. In contrast to the promising animal work with baclofen as an analgesic, our study in humans does not support the notion that baclofen is an analgesic.

Acetaminophen↗
PubMed1983

Effect of cinromide on inhibitory and excitatory mechanisms.

The effect of the experimental anticonvulsant cinromide (3-bromo-N-ethylcinnamamide) on various inhibitory and excitatory mechanisms was investigated in the trigeminal nucleus of cats. Intravenous administration of 20-80 mg/kg cinromide depressed excitatory transmission and facilitated segmental inhibition to the same extent as phenytoin, but less than carbamazepine. These doses of cinromide also depressed periventricular inhibition, similar to valproate and ethosuximide. In addition, cinromide had a marked depressant effect on the EEG, suggesting a pronounced sedative effect. The serum levels of cinromide and of its active metabolites (3-bromocinnamamide and 3-bromocinnamic acid) were comparable to those in patients receiving long-term treatment with cinromide. Our results agree with those in other experimental models, which also suggest that cinromide is a broad-spectrum anticonvulsant, and with cinromide's effect in the clinical trials reported so far.

Animals↗
PubMed1983

Effect of baclofen enantiomorphs on the spinal trigeminal nucleus and steric similarities of carbamazepine.

The seemingly structurally different drugs, baclofen and carbamazepine, have a similar neurophysiologic effect on the cat spinal trigeminal nucleus and a similar clinical effect in the amelioration of trigeminal neuralgia pain. In this investigation, we report on the enhancement of segmental inhibition by carbamazepine and l-baclofen; d-baclofen produced no effect on segmental inhibition. Doses of l-baclofen one fifth its equivalent racemic dosage produced a much greater enhancement of segmental inhibition. d-Baclofen, when given prior to l-baclofen, blocked the effect of l-baclofen on segmental inhibition and the unconditioned response at previously effective doses. Pretreatment with d-baclofen also blocked the effect of subsequent carbamazepine on segmental inhibition, but had no effect on the unconditioned response. Crystallographic evaluation of carbamazepine and the enantiomorphs of baclofen revealed a surprisingly good fit of baclofen isomers to moieties of the carbamazepine molecule. The results suggest that the baclofen enantiomorphs and carbamazepine have a common mechanism of action in the cat spinal trigeminal nucleus, and that d-baclofen, though inactive, is capable of interfering with the effect of l-baclofen and to a lesser extent with carbamazepine.

Animals↗
PubMed1982

Do phenytoin and carbamazepine depress excitation and/or facilitate inhibition?

The effect of phenytoin and carbamazepine on the segmental and the periventricular inhibition was investigated in interneurons of the spinal trigeminal nucleus oralis of cats. The segmental inhibition was elicited by delivering a conditioning stimulus to the maxillary nerve 100 ms prior to the test stimulus to the maxillary nerve, and the periventricular inhibition was elicited by delivering a conditioning stimulus to the periventricular gray matter. Therapeutic serum levels of phenytoin and carbamazepine facilitated the segmental inhibition, but depressed the periventricular inhibition, while also depressing the response of trigeminal nucleus neurons to an unconditioned maxillary nerve stimulus. These results indicate that the depression of neural activity by phenytoin and carbamazepine is selective, leaving some inhibitory pathways relatively untouched and thus greatly enhancing their effectiveness. It is suggested that the anticonvulsant properties of phenytoin and carbamazepine are due to their ability to produce a relative facilitation of inhibitory feedback mechanisms.

Animals↗
PubMed1981

Complications of baclofen withdrawal.

In three patients taking baclofen on a long-term basis, hallucinosis and/or seizures developed with abrupt reduction of dose or discontinuation of baclofen therapy. These cases emphasize the advisability of tapering the dose of baclofen gradually after long-term administration.

Adolescent↗
PubMed1981

Effect of anticonvulsant drugs on inhibitory and excitatory pathways.

A conditioning stimulus to the periventricular gray matter inhibits the response of spinal trigeminal neurons to maxillary nerve stimulation. Sodium valproate and ethosuximide decrease the periventricular inhibition without significantly affecting the response of these neurons to the unconditioned maxillary nerve stimulus. We have now found that carbamazepine and phenytoin decrease the response to the unconditioned maxillary nerve stimulus, and only depress the periventricular inhibition secondarily. These results further support the hypothesis that the ability to depress selectively inhibitory pathways in the CNS is an important characteristic of antiabsence drugs, and that absence seizures may represent paroxysmal discharges in inhibitory pathways.

Animals↗
PubMed1981

Role of inhibitory mechanisms in trigeminal neuralgia.

Segmental inhibition was elicited in the spinal trigeminal nucleus of cats by delivering a conditioning stimulus to the maxillary nerve 100 msec before the test stimulus. Carbamazepine, baclofen, and phenytoin markedly facilitated this segmental inhibition, as well as depressing the response to an unconditioned maxillary nerve stimulus. Phenobarbital, on the other hand, usually depressed the segmental inhibition. These results suggest that drugs that relieve trigeminal neuralgia both facilitate inhibitory mechanisms and depress excitatory mechanisms in the spinal trigeminal nucleus. The facilitation of inhibitory mechanisms appears to be at least as important as the depression of excitatory mechanisms and suggests that a failure of inhibitory mechanisms may play a significant role in the pathogenesis of trigeminal neuralgia.

Animals↗
PubMed1980

Baclofen in trigeminal neuralgia: its effect on the spinal trigeminal nucleus: a pilot study.

Experiments with cats showed that baclofen resembles carbamazepine and phenytoin sodium in its ability to depress excitatory synaptic transmission in the spinal trigeminal nucleus. Baclofen was, therefore, given to 14 patients with refractory trigeminal neuralgia. Ten patients were relieved of the paroxysms of tic douloureux while taking 60 to 80 mg/day of baclofen. A reduction in the dosage of baclofen in six of these patients resulted in a recurrence of painful paroxysms in five patients. Seven patients have been pain-free or almost pain-free on a regimen of baclofen for four to 12 months. Our results suggest that baclofen may be a useful drug in the treatment of trigeminal neuralgia and that our experimental model may successfully predict the efficacy of a drug in the treatment of this condition.

Adult↗