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Here we present the case of a 30-year-old woman with type I diabetes mellitus, preeclampsia and treatment resistant persistent hyperemesis gravidarum in her 25th week of gestation who was successfully treated with the antidepressant mirtazapine (Remergil). Nausea and vomiting resolved within 5 days. After discharge from the hospital in 28 weeks of gestation and discontinuation of the medication on her own initiative a relapse occurred, once again with good response to mirtazapine. The drug was continued until birth. At 34 + 0 weeks a cesarean section was performed due to fetal growth restriction and deteriorating preeclampsia. During the second and fourth day postnatal age the child temporarily developed hyperarousal which could be explained by mirtazapine withdrawal.

This study examined the effects of acute and chronic desipramine, 24-h total sleep deprivation (TSD) and 96-h REM sleep deprivation (REMSD) on physostigmine-induced hypothermia, analgesia and behaviour. The effects of acute and chronic desipramine treatment on oxotremorine-induced hypothermia were also examined. Intraperitoneal administration of physostigmine (0.5 mg/kg i.p.) induced hypothermia, analgesia, purposeless chewing movements (chewing) and head tremors. While atropine given in a low dose (1.0 mg/kg i.p. 15 min prior) did not antagonize the hypothermia, chewing and head tremor associated with physostigmine (0.5 mg/kg i.p.), a higher dose of atropine (10 mg/kg i.p. 15 min prior) decreased physostigmine-induced hypothermia, chewing and head tremor behaviour. Chronic (10 or 20 mg/kg i.p. daily for 10 days and withdrawn 24 h prior, chronic DMI) and acute (10 mg/kg, i.p. + 60 min prior, acute DMI) desipramine treatments abolished physostigmine (0.5 mg/kg i.p.)-induced hypothermia compared with saline pretreatment. Interestingly atropine (1 mg/kg i.p. 15 min prior) reversed the inhibitory effect of chronic DMI on hypothermia induced by physostigmine. Acute but not chronic DMI decreased physostigmine-induced chewing and head tremor behaviour. Atropine (1 mg/kg i.p. 15 min prior) increased the inhibitory action of acute DMI on physostigmine-induced chewing behaviour. Acute DMI (10 mg/kg i.p.) decreased oxotremorine (0.1 mg/kg i.p.)-induced hypothermia, while chronic DMI increased the hypothermic effect of oxotremorine. TSD and REMSD did not alter physostigmine (0.5 mg/kg i.p.)-induced hypothermia; however, REMSD and stress decreased physostigmine-induced analgesia and chewing.It is suggested that chronic desipramine treatment decreased physostigmine-induced hypothermia by causing hypersensitivity of pre-synaptic muscarinic receptors, whereas acute desipramine decreased the sensitivity of post-synaptic muscarinic receptors

The effects of nicotinic and beta-adrenergic receptor antagonists on tail-tremor induced by repeated nicotine administration were investigated in rats. The daily administration of nicotine (0.5 mg/kg/day, s.c.) for 8 days resulted in an augmentation of tail-tremor. However, repeated administration of dimethyl phenyl piperazinium iodide (1 mg/kg/day, s.c.) for 8 days did not cause tail-tremor. Mecamylamine (0.5 mg/kg, i.p), administered before the nicotine injection on each day, abolished the tail-tremor. After discontinuation of the mecamylamine treatment, nicotine injections caused tail-tremor augmentation. Propranolol (20 mg/kg, i.p.), administered before the nicotine on each day, suppressed the appearance of tail-tremor. After the discontinuation of propranolol treatment, the degree of tail-tremor induced by a single injection of nicotine on day 9 was much greater in the propranolol-treated group than in the saline-treated control group. Neither carteolol (20 mg/kg, i.p.) nor metoprolol (20 mg/kg, i.p.) treatment showed such effects. Intraspinal injection of 6-hydroxydopamine markedly enhanced the tail-tremor induced on the first day of nicotine injection. This effect became more intense on subsequent administration of nicotine. The enhanced tail-tremor following 6-hydroxydopamine treatment was abolished by mecamylamine (0.5 and 1 mg/kg, i.p.), and was suppressed by propranolol (5-20 mg/kg, s.c.) in a dose-dependent manner. These results suggest that central nicotinic receptors are essential for the onset and for the further development of tail-tremor induced by the repeated administration of nicotine, and that beta 2-adrenoceptors are associated with the tremor mechanism. Moreover, spinal noradrenergic mechanisms may be involved in the manifestation of this phenomenon.

The effects of two interventions, high ambient temperature, a sympathetic activator, and clonidine, a centrally acting sympatholytic drug, were compared on a number of autonomic functions. Eight healthy male volunteers participated in four weekly sessions. Each session was associated with one of the following treatments: placebo (physiological saline infused intravenously over 10 min) at 20 degrees C; clonidine hydrochloride (1.5 micrograms kg-1 in 10 ml infused intravenously over 10 min) at 20 degrees C; placebo at 40 degrees C; clonidine at 40 degrees C. Subjects were allocated to treatments and sessions according to a double-blind (for drug condition) balanced design. In each session, the following indices of autonomic function were recorded: systolic and diastolic blood pressure, heart rate, salivation, body temperature, plasma noradrenaline and adrenaline concentrations, baseline and carbachol-evoked sweating, physiological finger tremor. Raised ambient temperature (40 degrees C) caused increases in heart rate, body temperature, carbachol-evoked sweating and physiological finger tremor. Clonidine (at 20 degrees C) reduced systolic blood pressure, body temperature, salivation and plasma noradrenaline concentration, but did not affect any of the other measures. Clonidine (at 40 degrees C) counteracted the increase in heart rate, but not the increases in carbachol-evoked sweating and finger tremor, evoked by high ambient temperature. The high ambient temperature condition abolished the body-temperature-lowering effect of clonidine, but did not modify the effects of clonidine on systolic blood pressure, salivation and plasma noradrenaline concentration. These result indicate that while the effects of the heat stressor are consistent with an increase in sympathetic activity, and most of the effects of clonidine are consistent with a decrease in sympathetic activity, only two functions (body temperature and heart rate) were affected in opposite directions by the two interventions. Indeed physiological antagonism between the two interventions could be demonstrated on body temperature and heart rate only, and there was no evidence for an interaction between the effects of the two variables on any of the other indices of autonomic activity. The failure of clonidine to affect two sympathetically mediated functions, carbachol-evoked sweating and physiological finger tremor, under either temperature condition, indicates that central alpha 2-adrenoceptors cannot be involved in the regulation of these functions.

To test the hypothesis that altered neuronal activity may influence the extent and severity of the glio-vascular lesions produced by 1,3-dinitrobenzene (DNB), rats were either given the tremorgenic pyrethroid, Bifenthrin, or anaesthetised during various dosing schedules of DNB. When compared with controls dosed only with DNB, Bifenthrin tremor made both the ataxia and other functional effects caused by DNB more pronounced. Lesions in the brain stem were made significantly more severe and widespread across three dose levels of DNB. Centres such as facial nuclei, motor nuclei of fifth nerve, subthalamic nuclei and mamillary bodies, not damaged by DNB alone, were also affected in some animals. In contrast, general anaesthesia by either isoflurane ur urethane decreased the severity of the lesions, this being more pronounced with urethane. The character of the tissue changes, however, was not altered by these additional procedures. These findings support the suggestion that neuronal activity is one important determinant of the selective vulnerability of sensitive brain stem nuclei to glio-vascular damage from DNB intoxication.

A 58-year-old man with chronic paranoid-hallucinatoric psychosis had transient episodes with marked paranoid delusions, auditory hallucinations without confusion, shakiness of both upper extremities, tachycardia and sweating. EMG performed with surface electrodes revealed many silent periods in postural active muscles with maximum duration of 120 ms; blood glucose was 65-75 mg/dl. At other times, blood glucose was 135-140 mg/dl, EMG revealed few silent periods in postural active muscles with maximal duration of 50 ms and the patient noted some vibration in his outstretched hands only. Drug-induced asterixis (clozapine, benperidol) amplified by relative hypoglycemia was therefore assumed, and symptoms disappeared after oral antidiabetics were reduced.

Because of a depressive syndrome, a 39-year-old patient received 20 mg fluoxetine per day. Approximately 4 weeks later, treatment with this drug was stopped after the patient had complained of worsening tremor, particularly of the upper extremities. In addition, accommodation difficulties and problems with word-finding had appeared shortly before. The symptoms became worse after fluoxetine had been discontinued. Treatment of the side effects with piperiden and bromazepam brought about no real improvement in the patient's condition. The passive tremor with a frequency of approximately eight per second mainly suggests an extrapyramidal-parkinsonian cause. Five weeks after treatment with fluoxetine had been discontinued, owing to the persistence of the depressive syndrome the patient received maprotiline and clomipramine by infusion in a private hospital. After 2-3 days the patient complained of headaches and had a slightly raised temperature. After 7 days maprotiline and clomipramine were discontinued completely. During the fever there was no leucocytosis, so that a drug fever was diagnosed. These rare side effects are discussed.

To characterize the tail-tremor and locomotor hyperactivity induced by repeated nicotine administration, the effects of nicotinic, alpha-adrenergic and dopaminergic blockers were investigated in rats. Daily administration of nicotine (0.5 mg/kg, s.c.) induced tail-tremor from the 4th day, which became more marked in intensity by subsequent administration. Locomotor hyperactivity was also induced by nicotine, which was enhanced by daily administration. The tail-tremor and locomotor hyperactivity induced by repeated nicotine administration were inhibited by mecamylamine (0.1-1 mg/kg, i.p.) but not by hexamethonium (0.5 and 1 mg/kg, i.p.). Clonidine (0.02 and 0.04 mg/kg, i.p.) and prazosin (0.5 and 1 mg/kg, i.p.) reduced tail-tremor more markedly than hyperactivity. However, haloperidol (0.05-0.2 mg/kg, i.p.) and chlorpromazine (1-5 mg/kg, i.p.) reduced hyperactivity more markedly than tail-tremor. These results suggest that nicotine-induced tail-tremor and hyperactivity are due to an increased susceptibility of central nicotinic receptors of nicotine followed by catecholaminergic mechanisms, and that tail-tremor may be more associated with the noradrenergic system than the dopaminergic system.

A patient developed asterixis 13 weeks after starting a therapy with carbamazepine. Serum concentration of carbamazepine was within the therapeutic levels. Further factors which might have provoked asterixis were an impairment of pulmonary function and the combination with a neuroleptic and lithium. Since the latter risk factors had already been present for a long time, it may be assumed that the addition of carbamazepine triggered the development of asterixis.

1. The effect of various agents injected into the cerebral ventricles of the mouse, upon the tremor and hypothermia produced by oxotremorine (0.5 mg/kg i.p.) was studied. 2. Acetylcholine (0.1-10 mug) produced a dose-dependent potentiation of oxotremorine tremor in contrast to the multiphasic effect it had on the accompanying hypothermia. Both tremor and hypothermia were antagonised by very small doses (0.1-10 ng) of atropine. 3. Dopamine and apomorphine (0.1-10 mug) had no significant effect on oxotremorine tremor. A dose-dependent potentiation of hypothermia was, however, observed. 4. Noradrenaline (0.1-10 mug), phentolamine and propranolol (0.1-10 mug) produced no significant effect on tremor and inconsistent results were obtained on hypothermia. 5. Neither tremor nor hypothermia were affected by 5-hydroxytryptamine (1-20 mug). 6. Oxotremorine tremor appears to be due solely to the activation of cholinergic pathways, whereas the production of hypothermia is brought about via a system involving both cholinergic and dopaminergic components. 5-Hydroxytryptamine is not involved.

IK-6, a combination of the sympathomimetic fenoterol (low dose) and the anticholinergic ipratropium bromide (normal dose), was tested single-blind and cross-over in outpatients with intrinsic asthma and in healthy volunteers. In 12 patients IK-6 resulted in a good acute bronchodilatation, the onset was as quick as following fenoterol and the maximum was as good as following ipratropium bromide. In another 12 patients the protective effect against an acetylcholine-induced bronchoconstriction was better after IK-6 than after ipratropium bromide and much better than after salbutamol. In these patients IK-6 caused no unwanted side effects. In 10 healthy volunteers the effect on heart rate was tested after inhalation of 20 puffs of bronchodilators applied by metered dose inhaler. The anticholinergics (ipratropium bromide, oxitropium bromide, dibenzothiepine-derivative) caused no effect. Following fenoterol a marked increase in heart rate could be observed, whereas the combination IK-6 caused only a slight increase.

White Leghorn hens were fed diets containing 0, 300, 600, or 1200 ppm technical grade DDT for three 28-day periods. The 1200 ppm diet caused tremors and 33% mortality in the final period, but no gross toxicity symptoms were seen in birds fed the other diets. Egg production was decreased during the third period by 600 or 1200 ppm. Egg weight was decreased during the third period by 600 or 1200 ppm. Egg weight was decreased during the last two periods by 1200 ppm. Shell thickness was decreased in all three periods by feeding 600 or 1200 ppm DDT. Dietary DDT caused no change that could be detected by shell beta backscatter. Shell weight as a percent of total egg weight was decreased by 600 or 1200 ppm DDT.

Pro-Leu-Gly-NH2 (MIF) inhibits the tremor induced by oxotremorine. Objective measurement of this tremor permits the drawing of a dose-effect curve. The inhibitory effect of the peptide increases linearly with increasing doses until an optimum is reached (between 30 and 40 mg/kg i.p.). At still higher doses the peptide is inactive. The same phenomenon is observed with analogues of MIF. This finding may have important bearings on the interpretation of clinical and experimental data obtained with MIF.

LY 195448 is a phenethanolamine that has shown anti-tumour activity in a range of murine tumour models, although its mechanism of action is unknown. Pre-clinical studies have indicated the absence of "standard" side effects such as myelosuppression and gastrointestinal toxicity. The present phase I trial was carried out in nine patients at doses ranging up to 133 mg/m2. The major toxicities up to that dose were mild, reversible hypotension, tachycardia and tremor. No haematological or biochemical toxicity was observed. Murine pharmacokinetics were assessed at a dose level that was effective in experimental tumours and compared with human pharmacokinetic parameters derived from this study. The results indicated the clinical possibility of reaching peak drug levels associated with experimental activity. However, no responses were seen at the doses used. This study was terminated prior to its completion due to an unexplained loss of activity against murine tumours since September 1987. No significant loss of the in vitro anti-mitotic activity originally reported by Boder et al. [3] was observed. Possible reasons for the apparent loss of in vivo activity have been intensively investigated, but no cause has been determined. Therefore, clinical trials with LY 195448 have been discontinued.

Changes of local cerebral glucose consumption under the effect of tremogenic doses of harmaline were studied. To find the brain structures activated by the drug, the autoradiographic method using [14C]2-deoxyglucose was applied to young cats. After administration of harmaline, the animals were paralized with flaxedil. Results were compared to a group of control animals not injected with the drug, but submitted to the same experimental protocol. Increases of neuronal activity were observed in several structures. A) Among the relays of the olivo-cerebello-fastigio (and vestibulo)-reticulo-spinal circuit that had been claimed to fire at the frequency of the tremor, labeling was found in: 1. selected portions of the inferior olive including the medial accessory olive and the caudolateral part of the dorsal accessory olive; 2. the molecular layers of the cerebellar cortex including vermian and paravermian zones. Labeling of the olivo-cerbellar system was therefore larger than the compartment controlling the fastigial nucleus and extended to that controlling the interpositus nucleus. B) Other structures not under the direct control of the olivo-cerebellar system displayed increased radioactivity under harmaline: lateral reticular nucleus, nucleus reticularis tegmenti pontis, red nucleus and basal ganglia. Part of the nucleus ambiguus, intensely labeled in the control animals, showed decreased radioactivity under harmaline. The experiments were repeated with the same protocol in another group of animals with unilateral sections of the inferior cerebellar peduncle in order to distinguish between a direct pharmacological influence and a nervous one. Marking of the basal ganglia was not affected by pedunculotomy, suggesting a direct "pharmacological" action of the drug in this cases. On the other hand, marking of the other labeled structures was asymmetric or suppressed by pedunculotomy, and therefore could result from a "nervous" effect secondary to activation of the inferior olive.

Purkinje cells were recorded extracellularly and mapped in the cerebellar cortex of the rat under tremogenic doses of harmaline. Four different types of responses were encountered, of which two were considered as being responsible for the harmaline tremor. The latter had a regular firing pattern of complex spikes at 5 to 10 Hz and were mostly found in the vermis. Their number decreased in the more lateral region of the cerebellar cortex until they eventually disappeared. Horseradish peroxidase was injected into all the areas of the cerebellar cortex containing Purkinje cells with harmaline-induced activity. Labeled neurons were in all cases traced to the medial accessory olive. The metabolic activity of the inferior olive under harmaline was measured with 2-deoxyglucose. Increased labeling was only found in the medial accessory olive. Such an increase was demonstrated as being due to a direct effect of the drug on the inferior olivary neurons, indicating that the medial accessory olive is responsible for the harmaline tremor in the rat. Our results point out that, in the rat, there is an inverse relationship between serotoninergic innervation of a region in the inferior olivary nucleus and that with harmaline sensitivity, therefore a serotoninergic mechanism hypothesis for the harmaline tremor needs further investigation.

Both TRH and quipazine (2.5-25 mg/kg) were found to restore and to intensify the oxotremorine-induced tremor in mice when injected i.p. 60 min after oxotremorine 0.5 mg/kg s.c. This phenomenon does not seem to be due to an increase in body temperature or muscle tone. Also other dopaminergic drugs, e.g. amphetamine, methylphenidate, nomifensine and apomorphine had a significant but lesser effect than TRH or quipazine. Haloperidol and methysergide both antagonized the effect of quipazine but not that of TRH. Neither propranolol, phenoxybenzamine, alpha-methyl-p-tyrosine, nor p-chlorophenylalanine inhibited the activity of TRH or quipazine. The restoration of oxotremorine-induced tremor could be prevented by atropine but not by methylatropine. It is concluded that quipazine exerts its effect by direct stimulation of serotoninergic and dopaminergic receptors, whereas TRH receptors may represent separate entities and TRH may function as a neurotransmitter or neuromodulator.

Units were recorded extracellularly in the cat brainstem under the effect of tremogenic doses of harmaline. They were localized post mortem and the units discharging at the harmaline tremor frequency were mapped. Harmaline-sensitive neurons were found in the bulbo-pontine reticular formation, in particular, in the lateral reticular nucleus and the nucleus reticularis tegmenti pontis. The nucleus interpositus as well as the red nucleus also displayed numerous units discharging at the tremor frequency, indicating that the cerebello-interposito-rubro-spinal system controlling the flexor muscles participate in harmaline tremor. Participation of the oculomotor system in the harmaline-induced tremor was tested at the level of the vestibular neurons relaying the vestibulo-ocular reflex, the motoneurons, the eye muscles and the eye movements. No rhythmic discharge at the tremor frequency nor eye movements could be detected, indicating that harmalie tremor does not affect the oculomotor system.

Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effect of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.

The muscarinic receptor affinity of 27 psychotropic and 5 anticholinergic substances was examined in 2 in-vivo and 2 in-vitro models. A highly significant correlation was obtained between the effect of all compounds examined on the atropine sensitive binding of 3H-PrBCM and the effect in the conventional guinea-pig ileum preparation. Antagonism of oxotremorine induced tremors in mice by anticholinergics and neuroleptics was also significantly correlated to the corresponding data obtained in the in-vitro tests. Due to very low potency in the physostigmine induced mortality test in mice too few ED50 values were obtained to perform statistical comparisons. It is concluded, that the conventional guinea-pig ileum model and the 3h-prBCM binding model are equally predictive as tests for antimuscarinic properties. When in-vivo anticholinergic data for neuroleptics are used it must be considered that a possible dopamine receptor blockade may diminish the antimuscarinic effect of the substance.

Developing chick embryos were exposed to streptomycin injected on days 5 through 13 of the 21 day developmental period. Histological and behavioral abnormalities were found almost exclusively in chicks exposed after day 7. The nature of the behavioral deficits included abnormal head posture, head tremor, and inability to compensate for applied vestibular stimuli. Head movement measurements showed that the head tremor had frequencies of oscillations from 10-35 Hz. The amplitude of the tremor was a large as 10 degrees. Histology showed damage to the secretory dark cells of the membranous labyrinth in those chicks that showed behavior changes. Even with increased dosages chicks exposed prior to day 7 rarely showed abnormal vestibular behavior but instead experienced increased mortality. Further tests examining tissue levels of streptomycin showed little or no streptomycin in embryos until day 10. These results are discussed in terms of their utility as an alternative model to surgical manipulation of the vestibular system in developing embryos. Behavioral consequences are compared to other work with drugs and to the effects of weightlessness and unusual environments on vestibular orientation and behavior.

The cholinomimetic activities of the antidepressant drug minaprine have been investigated, in vitro and in vivo, in rodents. Minaprine, and its metabolite SR 95070B [3-(2-morpholinoethylamino)-4-methyl-6-(2-hydroxyphenyl) pyridazine hydrochloride] selectively displaced [3H]-pirenzepine from its cortical and hippocampal binding sites, and only weakly inhibited the binding of [3H]-N-methylscopolamine in either the rat cerebellum, heart and salivary glands, or the guinea-pig ileum. In mice, none of these drugs induced the typical cholinergic side-effects up to lethal doses. Minaprine and SR 95070B antagonized rotations induced by an intrastriatal injection of pirenzepine in mice, after intraperitoneal and/or oral administration. Minaprine also antagonized atropine-induced mydriasis in mice. Both minaprine and SR 95070B potentiated the tremorigenic effect of oxotremorine without inducing tremor when injected alone. Finally, minaprine and SR 95070B, after parenteral and/or oral injection, antagonized the scopolamine-induced deficit in passive avoidance learning, and enhanced short-term retention in the social memory test, in rats. The muscarinic agonists arecoline, oxotremorine and RS 86 [2-ethyl-8-methyl-2,8 diazaspiro-4,5 decan-1,3 dion hydrobromide], as well as the acetylcholine esterase inhibitors physostigmine and tacrine were active in most of these models. These results indicate that minaprine, and its metabolite SR 95070B, have cholinomimetic activities which could be, at least in part, mediated by their selective affinity for M1 muscarinic receptors. Thus minaprine could represent a potential useful drug for the treatment of senile dementias and cognitive impairments occurring in elderly people.

1-Tryptophan was administered to rats pretreated with selective inhibitors of the A and B forms of MAO deprenyl, a selective inhibitor of MAO-B, produced minor changes in behaviour and in the concentrations of apparent 5-HT and 5-HAA in brain. High doses of clorgyline, a selective inhibitor MAO-A, produced a characteristic stereotyped syndrome of hypermotility and tremor as well as an increase in apparent 5-HT and a decrease in apparent 5-HIAA in brain. Small doses of deprenyl and clorgyline in combination, but not singly, produced maximal effects on behaviour as well as on the concentrations of apparent 5-HT and 5-HIAA in brain. Maximum behavioural and biors before the other. It is concluded that the syndrome may be dependent on the formation of an N-substituted derivative of 5-HT which is at least partly deaminated by MAO-B. Alternatively, the syndrome may be dependent on a sufficiently high concentration of 5-HT in a special compartment where it is partly deaminated by MAO-B.

The effects of anticholinergic and dopaminergic drugs used for Parkinson's disease were studied on the tremor induced by physostigmine (0.3-3.0 mg/kg) in rats. For the measurement of tremor a new electronic device was employed. Atropine (0.3-1.2 mg/kg) and biperiden (0.01-1.0 mg/kg) reduced the physostigmine-induced tremor in a dose-related manner and could abolish it. Biperiden was less potent than atropine. Methylatropine in a dose of 1.2 mg/kg slightly inhibited the tremor. Amantadine (0.3-3.0 mg/kg) reduced the tremor but only to a certain degree. Bromocriptine (0.1-10.0 mg/kg) reduced it in a manner that was not dose-related. Pimozide potentiated the tremor in the dose of 0.2 mg/kg but not in larger doses. At the onset of the tremor, a small decrease in rectal temperature occurred. The hypothermia lasted significantly longer than the tremor. Neither the anticholinergic nor the dopaminergic anti-Parkinson drugs altered the hypothermic effect of physostigmine. The results show that those anti-Parkinson drugs, which act by increasing the dopaminergic activity can counteract the tremor induced by physostigmine. However, these drugs are clearly less active than th anticholinergic anti-Parkinson drugs.

A method permitting measurement of finger tremor as a displacement-time curve is described, using a test system with simple amplitude calibration. The coordinates of the inversion points of the displacement-time curves were transferred through graphical input equipment to punched tape. By means of a computer program, periods and amplitudes of tremor oscillations were calculated and classified. The event frequency for each class of periods and amplitudes was determined. The actions of fenoterol-hydrobromide, ritodrin-HCl and placebo given to 10 healthy subjects by intravenous infusion in a double-blind crossover study were tested by this method. At therapeutic doses both substances raised the mean tremor amplitude to about three times the control level. At the same time, the mean period within each class of amplitudes shortened by 10--20 ms, whereas the mean periods calculated from all oscillations together did not change significantly. After the end of fenoterol-hydrobromide infusion, tremor amplitudes decreased significantly faster than those following ritodrin-HCl infusion.