Matters arising 427 tive sleep apnoea and they had also had sleep in Parkinson's disease (PD) with the effects.2 Despite some experimental data, recordings to confirm the diagnosis. Snoring NMDA antagonist ifenprodil were report- the respective role of these different phar- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.4.427-a on 1 April 1993. Downloaded from can be considered as a subocclusive stage of ed. Ifenprodil acts at the polyamine binding macological mechanisms remains unknown obstructive sleep apnoea but not all snorers site of the NMDA receptor. The authors to explain the clinical anti-Parkinsonian develop it. It is possible that the muscles in state "this drug is, as far as we know, the properties of these drugs. Amantadine has the pharynx are affected in different ways sole NMDA antagonist currently available only a weak and transient clinical anti- during different stages of the disease. on the market", and "our study is the first Parkinsonian efficacy which may be com- In the specimens from all patients with to investigate the clinical effects of an patible with a weak dopamine effect. There obstructive sleep apnoea we found promi- NMDA antagonist in the treatment of PD". are mainly speculative links between the nent neurogenic changes with signs of both The adamantanamines amantadine and anti-NMDA and the anti-Parkinsonian denervation and reinnervation. In such memantine have been used since 1969 in effects of amantadine. In our opinion, it cases we found analysis of the fibre type the treatment of PD.2-4 The weak dopamine is therefore still premature to support spectra to study fibre type adaption less rel- agonism in experimental studies seems Komhuber and Riederer, because of the evant. Subtypes of fibre type II (a, b and c) insufficient to account for their clinical amantadine and memantine data only, that were identified but showed a great variation effects.45 It has been shown recently that "NMDA antagonists are used successfully and a further analysis was not considered amantadine and memantine act at the PCP for many years in the treatment of PD". necessary in the limited number of subjects. binding site of the NMDA receptor-coupled This is why we were interested in investigat- Our morphometry did not show "a great ion-channel." It is therefore concluded ing the clinical effects of another drug, such variability of muscle fibre size" or atrophy that: 1) there are other NMDA antagonists as, ifenprodil, which does not have as interpreted by lannaccone et al. The fibre clinically available besides ifenprodil and 2) dopamine effects. size distribution showed similar abnormali- NMDA antagonists have been used success- It is perfectly clear, as we had already ties in all patients, mostly with a two peak fully for many years in the treatment of PD. stated in our first letter,' that "our work dispersion which is typical for a neurogenic The disappointing results with ifenprodil does not exclude a definite role for NMDA lesion. do not therefore argue against the newly antagonists in PD" because of the negative The muscle specimens were obtained proposed "glutamate hypothesis" of PD,78 ifenprodil data. We had also already written during surgery from the same part of the but may be related to: 1) the pharmaco- that other NMDA antagonists with better cranial portion of the palatopharyngeal mus- kinetic profile of the drug'; 2) a rather weak pharmacodynamic or pharmacokinetic pro- cle in all patients and controls. The muscle influence of polyamine binding site antago- file may be effective.' Since our results have was exposed after the tonsil had been nists compared with ion-channel blockers been published, we know that there is removed. The same surgeon (HL) collected on NMDA receptor function or 3) a patho- another NMDA antagonist which is avail- or supervised the collection of all specimens. logically altered polyamine binding site in able in clinical practice. A recent open We consider our finding of a neurogenic PD. These points have to be examined in study has suggested that dextromethorphan, lesion in the palatopharyngeal muscle in future studies. an antitussive drug that is also a non com- J KORNHUBER petitive antagonist of the NMDA receptor, patients with obstructive sleep apnoea to be P RIEDERER correct. The same type of lesions have been Department ofPsychiatry, might have some efficacy in PD.3 described by Woodson et all in the uvular University of Wurzburg, JL MONTASTRUC muscle of these patients. Recently we have Fachsleinstrafie 15, 0 RASCOL 8700 Wurzburg, Germany JM SENARD published a study showing affected sensory Departments ofMedical pharyngeal nerves in obstructive sleep Correspondence to: Dr Kornhuber. and Clinical Pharmacology apnoea patients.6 A RASCOL 1 Montastruc JL, Rascol 0, Senard JM, Rascol Department ofNeurology, We believe the different findings in the A. A pilot study of N-methyl-D-aspartate Iannaccone et al' are due to a dif- Centre Hospitalier Universitaire, study by (NMDA) antagonists in Parkinson's disease. Faculte de Medecine, ferent biopsy site being examined and that J Neurol Neurosurg Psychiatry 1992;55: 37 alkes Judes-Guesde, the patients were not suffering from 630-1. 31073 Toulouse Cedex, France obstructive sleep apnoea. Whether the type 2 Parkes JD, Zilkha KJ, Calver DM, Knill-Jones RP. Controlled trial of amantadine hydro- 1 Montastruc JL, Rascol 0, Senard JM, Rascol of abnormalities described in the MPC chloride in Parkinson's disease. Lancet 1970; A. A pilot study of N-methyl-D-Aspartate muscle by Iannaccone et al are present also i:259-62. (NMDA) antagonists in Parkinson's disease. 3 Fischer PA, Jacobi P, Schneider E, J Neurol Neurosurg Psychiat 1992;55:630-1. in the palatopharyngeal or uvular muscle of Schonberger B. Die Wirkung intravenoser snorers remains to be studied. 2 Lang AE, Blain RDG. Anticholinergic Drugs Gaben von Memantin bei Parkinson- and Amantadine in the treatment of HAKAN LARSSON Kranken. Arzneimittel-Forsch/Drug Res 1977; Parkinson's disease. Handb Exp Pharmacol http://jnnp.bmj.com/ LARS EDSTROM 27:18-20. 1989;88:307-23. LARS LARSSON 4 Kornhuber J, Streifler M. Adamantanamine. 3 Bonucelli U, Del Dotto P, Piccini P, Benge F, Sronkliniken, Sodersjukhuset, In: Riederer P, Laux G, Poldinger W, Corsini GU, Muratorio A. Dextrometh- S- 18 83 Stockholm, Sweden eds. Neuro-psychopharmaka, vol 5. Vienna: orphan and Parkinsonism. Lancet 1992; Springer, 1992:59-76. 340:53. 1 Smime S, lannaccone S, Ferini-Strambi L, 5 Kornhuber J, Bormann J, Hubers M, Rusche Comola M, Colombo E, Nemni R. Muscle K, Riederer P. Effects of I-amino-adaman- fibre type and habitual snoring. Lancet tanes at the MK-801-binding-site of the ion channel. A 1991;337:597-9. NMDA-receptor-gated in TIAs with a cerebral 2 Hillerdal G, Hetta J, Lindholm C-E, human postmortem brain study. Eur J Risk of stroke Hultcrantz E, Boman G. Symptoms in Pharmacol [Mol Pharmacol Sect] 1991;206: infarct on CT on September 29, 2021 by guest. Protected copyright. heavy snorers with and without obstructive 297-300. sleep apnea. Acta Otolaryngol (Stockh) 6 Kornhuber J, Bormann J, Retz W, Hubers M, I have read the article by Koudstaal et at in 1991;111:574-81. Riederer P. Memantine displaces ['H]MK- which the authors find a relevant ischaemic 3 Viner S, Szalai JP, Hoffstein V. Are history 801 at therapeutic concentrations in post- and physical examination a good screening mortem human frontal cortex. Eur J lesion on CT in 13% of TIAs, 35% of test for sleep apnea? Ann Intern Med Pharmacol 1989;166:589-90. RINDs and 49% of minor stroke. In their 1991;115:356-9. 7 Klockgether T, Turski L. Excitatory amino acids and the basal ganglia: implications for wide bibliographic review they only mention 4 Crocker BD, Olson LG, Saunders NA, on Hensley MJ, McKeon JL, Allen KM, Gyulay the therapy of Parkinson's disease. Trends one comparative study infarction charac- SG. Estimation of the probability of dis- Neurosci 1989;12:285-6. teristics between patients with transient and turbed breathing during sleep before a sleep 8 Riederer P, Lange KW, Kornhuber J, persisting signs.2 We reported four years ago study. Am Rev Respir Dis 1990;142:14-8. Danielczyk W. Glutamatergic-dopaminergic similar results in 219 patients with 5 Woodson BT, Garancis JC, Toohill RJ. balance in the brain. Its importance in Histopathologic changes in snoring and motor disorders and schizophrenia. reversible ischaemic attacks demonstrating obstructive sleep apnea syndrome. Laryngo- Arzneimittel-Forsch/Drug Res 1992;42:265-8. that the frequency of brain infarction was scope 1991;101:1318-22. related to the duration of the neurological 6 Larsson H, Carlsson-Nordlander B, Lindblad Montastruc et al Ischaemic lesions on CT LE, Norbeck 0, Svanborg E. Temperature reply: deficit.' closely thresholds in the oropharynx of patients We acknowledge Drs Kornhuber and correlated with abnormalities on supra- with obstructive sleep apnea syndrome. Am Riederer's comments conceming our trial aortic trunk angiography or Doppler ultra- Rev Respir Dis 1992;146:1246-9. on ifenprodil in Parkinson's disease (PD).' sonography. A higher percentage of recur- We are well aware that the adaman- rence was found in those patients with N-Methyl-D-Aspartate (NMDA) anta- tanamines amantadine and memantine have infarctions, but the difference was not sig- gonists in Parkinson's disease anti-NMDA properties but amantadine is nificant. also known to release dopamine from stri- Koudstaal et al mentioned the possibility We would like to comment on the letter by atal neurons, to inhibit the reuptake of of an increased risk of major stroke in TIAs Montastruc et alt in which negative results dopamine and to have anticholinergic with cerebral infarct on CT.' Using our pre-