A novel substance associated with gallamine-induced myoclonus.

If gallamine or d-tubocurarine gains access to the central nervous system it produces a myoclonus, a synchronized jerking of many skeletal muscles. Each jerk is accompanied by a slow wave in the inferior olive. The jerking continues for 24 h or more after the gallamine or d-tubocurarine can no longer be detected in the CSF. We report here that a novel substance appears in the CSF and persists for a long period of time, possibly as long as the twitching. This substance is not corticotrophin-releasing factor (CRF) nor does CRF or harmaline (a substance causing a tremor by an action on the inferior olive) lead to the appearance of the novel substance. At present the nature of this substance is not known.

Myoclonus in the decerebrate cat produced by gallamine.

After intravenous infusion maintaining a neuromuscular blocking concentration very little gallamine enters the cerebrospinal fluid (CSF) of the intact anesthetized cat even after several days. After a similar intravenous infusion in the decerebrate cat gallamine enters the CSF slowly over 4 days eventually reaching a concentration similar to that in the plasma. This procedure is accompanied by very strong twitching in many muscles and the occurrence of slow waves in the inferior olive in synchrony with the twitches. A large dose (4 mg) of gallamine triethiodide injected directly into the cisterna magna of an intact anesthetized cat produced twitching within 1 min and slow waves in the inferior olive in good synchrony with the twitches; the effects lasted at least 43 h. Injection of a quantity of gallamine triethiodide (about 130 micrograms) sufficient to mimic the concentration in the CSF obtained after 3-4 days of neuromuscular block in the decerebrate cat (50-120 micrograms/ml gallamine) had extremely weak effects lasting for at most 1 h. However, this weak effect is probably due to the anesthetic because injection of a similar quantity into an (unanesthetized) decerebrate cat at any time after decerebration had strong effects. After intracisternal injection of gallamine the concentration in the CSF reaches very low levels within 12 h but twitching and activity in the inferior olive persists for 1-2 days. The reasons for this prolonged action are now being investigated. The effects of gallamine are compared with the condition of reticular reflex myoclonus.

Accidental subarachnoid injection of gallamine. A case report.

Accidental subarachnoid injection of gallamine and its management is reported. Methods of identification of the drug in the c.s.f. are described. Early treatment should be initiated, since the drug was still identifiable in the c.s.f. after 90 min. Removal of the c.s.f. and sedation may have prevented a fatal outcome in our patient.

Passage of gallamine from blood into the liquor space in man and in dog.

1. Patients receiving an intravenous injection of 2-3.8 mg/kg gallamine showed gallamine-like activity in their lumbar c.s.f. collected 15 and 70-100 min after the injection. The activity assayed on acetylcholine contractions of frog rectus muscle was equivalent to between 0.1 and 0.75 mug/ml gallamine.2. In anaesthetized dogs an intravenous injection as well as an intravenous infusion of gallamine led to the appearance of gallamine-like activity in the cisternal c.s.f. and, on perfusion of the cerebral ventricles, in the effluent collected from the cisterna magna.3. After an intravenous injection of 1 mg/kg the activity in the cisternal c.s.f. corresponded to between 0.2 and 1 mug/ml and in the effluent to between 130 and 175 ng/min during the first 15 min perfusion and then declined.4. On intravenous infusion of gallamine at a rate of 10 (mug/kg)/min for 2 h the cisternal c.s.f. showed a uniform gallamine-like activity corresponding to between 0.4 and 0.67 mug/ml during the infusion. In the cisternal effluent the gallamine-like activity rose initially to between 20 and 90 ng/min but declined before the infusion was ended.5. The intravenous injection of gallamine caused respiratory paralysis but did not affect arterial blood pressure; its intravenous infusion caused no respiratory paralysis and did not affect arterial blood pressure.