Antivertigo Drugs Research Articles

The use of vestibular tests for the selection of anti-vertigo drugs.

Vertigo is not a disease, but a symptom. Therefore, the therapy of vertigo is primarily directed at eliminating the underlying cause. In about half of the cases the cause will not become apparent, however, and the therapy is doomed to be symptomatic. Several types of drugs have been found to have an anti-vertigo activity, e.g. antihistamines, calcium antagonists, anti-emetics. For the selection of vestibular depressants, the vestibular caloric test and the rotation test can be used. The duration of the nystagmus induced by rotation is the most useful parameter. The lag-period, the extent and duration of the vestibular effects can be determined and compared with that of other substances. A stronger action on a nystagmus does not necessarily mean a stronger anti-vertiginous action. The final proof of an anti-vertiginous activity can only be established in clinical studies in patients with vertigo.

塩酸ジラゼプのめまいに対する臨床成績

The effectiveness of Dilazep hydrochloride (Comelian Kowa) was tested in 84 patients with vertigo (14 with central vertigo, 50 with peripheral vertigo, and 20 with so-called vertigo).1. Improvement occurred in 85.2% ofthose with central vertigo, in 92% of those with peripheral vertigo, and in 78.9% of those with so-called vertigo.2. Subjective symptoms began to be relieved and objective findings improved as global improvement ratings and global utility ratings rose 2 weeks after the start of treatment. The ratings were significantly improved at 4 weeks and at 8 weeks, but no difference was observed between the 4 weeks and 8 weeks evaluations.3. Antivertigo drugs were avoided, in general, but tranquilizers were administered in a few cases. There was no significant difference between the group given combined theraphy and that given Dilazep only; improvement rates were 90.9% and 86.1%, respectively.4. The improvement rate in patients below 50 years of age was 80.5% and that in patients over 50 years of age was 95.2%.5. Adverse reactions occurred in 4 patients(4.8%), but they were mild.

Experimental Vestibular Pharmacology: A Minireview with Special Reference to Neuroactive Substances and Antivertigo Drugs

Neurotransmitters and neuromodulators involved in the function of vestibular nuclei were reviewed with special reference to drugs used for treatment of motion sickness and vertigo. Biochemical, histochemical and electrophysiological studies have demonstrated that acetylcholine is a transmitter candidate from the afferent vestibular nerve to the lateral vestibular nucleus (LVN), because acetylcholine satisfies most criteria for a chemical transmitter in the central nervous system. It is unlikely, however, that monoamines such as noradrenaline, dopamine and serotonin are transmitters in the vestibular neurons, since cell bodies and nerve terminals containing the monoamines have not been detected yet in the vestibular nuclei. Although histamine and H1-receptor blockers inhibit neuron activities in the vestibular nuclei, it is unclear at present whether histaminergic system is directly related to the function of vestibular neurons. It has been established that GABA is an inhibitory transmitter from the cerebellar Purkinje cells to the LVN neurons. Diazepam is considered to enhance the GABA effect on the LVN, thereby modifying the vestibular neuronal firing. Enkephalin-containing cell bodies and nerve terminals are found in the medial vestibular nucleus, and a few substance P-containing neurons have been observed in the vestibular nuclei. However, the functional role of these peptides on the vestibular system remains to be determined. Unlike histamine H1-receptor blockers, vasodilators such as cinnarizine, ifenprodil and adenosine triphosphate, which are effective in treatment of vertigo, produce an enhancement of responsiveness of neuron activities in the vestibular nuclei, probably as a result of an increase in blood flow in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effect of betahistine on polysynaptic neurons in the lateral vestibular nucleus.

Effects of betahistine, an antivertigo drug, were examined on the lateral vestibular nucleus (LVN) neurons of cats anesthetized with alpha-chloralose. Spike generation of monosynaptic LVN neurons elicited by vestibular nerve stimulation remained unaffected with intravenous administration of betahistine up to 5 mg/kg and with iontophoretic application of the drug up to 200 nA. In contrast, the spike generation of polysynaptic I neurons in the LVN was dose-dependently inhibited by intravenous as well as iontophoretic application of betahistine. These results suggest that small doses of betahistine more selectively interfere with synaptic transmission in the polysynaptic I neurons than in the monosynaptic neurons.

前庭薬理学 Ｖｅｓｔｉｂｕｌａｒ Ｐｈａｒｍａｃｏｌｏｇｙ

The paper deals with recent advances in anatomical, physiological, biochemical and pharmacological studies on the vestibular system. Fiber connections and characteristics of neurons in the vestibular nuclei were discussed in relation to regulation from other structures such as the cerebellum, oculomotor nuclei, reticular formation and spinal cord. In addition, a review was made of the actions on the vestibular system of antivertigo drugs including anticholinergic and antihistamine drugs, tranquilizers and barbiturates. All the obtained data show that the vestibular nuclei are devoid of noradrenergic, dopaminergic and serotonergic innervation, in contrast to other brainstem nuclei. Acetylcholine is apparently a neurotransmitter in the afferent transmission from the vestibular nerve to the vestibular nuclei. Antivertigo drugs produce modification in the neuron activity in the medial and lateral vestibular nuclei.

Effects of ifenprodil on lateral vestibular nucleus neurons in the cat (author's transl)

Electrophysiological studies were performed to elucidate effects of ifenprodil, an antivertigo drug, on neuron activity in the lateral vestibular nucleus (LVN) of cats anesthetized with alpha-chloralose. LVN neurons were classified into three types, according to the response pattern upon vestibular nerve stimulation: monosynaptic, polysynaptic I and polysynaptic II neurons, which fired spikes with the mean latencies of 1.07 +/- 0.12 (n = 6), 2.20 +/- 0.19 (n = 8) and 16.37 +/- 2.11 msec (n = 7), respectively. Intravenous administration of ifenprodil up to 5 mg/kg did not affect spike generation of monosynaptic neurons. Spike generation of polysynaptic I and II neurons was dose-dependently inhibited by ifenprodil up to 1 mg/kg. However, increasing doses of the drug up to 5 and 10 mg/kg produced complex effects such as an enhancement of the inhibitory effect in some neurons or a facilitation of responses in others. These results indicate that ifenprodil acts on the polysynaptic I and II neurons without affecting the monosynaptic neurons. It is likely that a small dose of ifenprodil may directly inhibit polysynaptic neurons and higher doses may indirectly enhance the responsiveness of the neurons, probably as a result of an increase in blood flow in the vertebral artery.

Clinical Application of Evoked Electromyography (Frequency Depression Curve) in the Diagnosis and Treatment of Vertigo

For the purpose of determining how abnormal myogenic tonus of the skeletal muscles is involved in the mechanism of vertigo and equilibrium disturbances and investigating whether the classification of antivertigo agents would be possible electro myographically, evoked electromyography by H-reflex of the gastrocnemius muscle was applied to the cases complaining of vertigo and equilibrium disturbances and their frequency depression curves (hereinafter referred to as FDC) were investigated. Two hundred and twenty nine patients who visited the Otolaryngological Department of Osaka University during the period from June 1971 to November 1975, complaining of vertigo and equilibrium disturbances were examined. In the cases of vertigo, FDCs of rigid, rigospastic or spastic type, reflecting hypertonic myogenic tonus of the gastrocnemius muscle, or FDCs of cerebellar type reflecting hypotonic myogenic tonus were seen, and both FDCs of the right and left gastrocnemius muscle were found to be widely different. In the patients complaining of body sway, the rigid type of FDC was recognized and in the cases of equilibrium disturbances, the cerebellar type of FDC was observed. In 80 % of the cases having attacks of vertigo, abnormal types of FDC were observed, differing between right and left legs. On the other hand, in the remission period of attacks, the normal type of FDCs with less difference between legs was observed. There were found correlations between the type of FDCs showing the myogenic tonus abnormality of the gastrocnemius muscle and the results of body deviation tests. It was assumed that the classification of types of FDCs will be of use for the search for suitable antivertigo drugs effective in the treatment of various vertiginous conditions and equilibrium disturbances.

Effect of drugs on after-nystagmus induced by lateral vestibular nucleus stimulation.

A BRIEF TRAIN of electrical stimulation to the lateral vestibular nucleus to elicit nystagmus lasting for a considerable time poststimulation in cats has been reported by Yules and Gault.¹This response is quite predictable over several hours (Fig 1). Considering that this response exists poststimulation and that it is a predictable event, it appears that nystagmus elicited in this way might serve as a valuable assay procedure for antivertigo drugs. The effects of medication on nystagmus have been evaluated previously using caloric, galvanic, or movement stimulation as the eliciting agent, but there have been no reports of the evaluation of medication on nystagmus elicited by central vestibular stimulation. <h3>Methods</h3> Experiments were performed on 29 cat preparations. Under ether anesthesia, the animals were tracheostomized, had a cephalic vein catheter inserted, underwent an occipital craniectomy, and had the spinal cord sectioned at C₁. Wound edges were infiltrated with procaine and