Pharmacological Aspects of Parkinsonism

Friedman, Alexander H.; Everett, G. M.

doi:10.1016/s1054-3589(08)61111-4

Cited by 48 publications

(7 citation statements)

References 142 publications

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“…The significant decrease in 5-HT levels during the light phase of the illumination cycle following pretreatment with pentobarbitone sodium suggests either an increase in utilization of 5-HT during barbiturate sleep and/or a net decrease in 5-HT synthesis. The latter might be due to a decrease in body temperature resulting in a slowing of the circulatory processes and enzymic activity (Friedman & Everett, 1964). The average difference in rectal temperature between control and treated rats observed during the dark phase of the illumination cycle was 2.54°, whilst the average difference noted during the light phase was only 0.780 C. The decrease in body temperature in the pentobarbitone treated animal is in part the result of decreased motor activity and depressed metabolic activity.…”

Section: Discussionmentioning

confidence: 90%

Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium

Friedman¹,

Walker²

1969

The Journal of Physiology

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1. The circadian patterns for onset and duration of sleep after the administration of a constant dose of pentobarbitone sodium have been measured in rats adapted to and maintained under a fixed illumination cycle. The relationship of these patterns to others for rectal temperature and motor activity as well as for noradrenaline (NA), 5‐hydroxytryptamine (5‐HT) and histamine in mid‐brain and caudate nucleus, and histamine and glucose in blood serum, has been examined. 2. The onset of sleep is longest and duration shortest during the phase of the illumination cycle when motor activity and rectal temperature are maximal. An inverse relationship for these parameters is found during the light phase of the illumination cycle. 3. In untreated rats, mid‐brain NA and histamine and caudate nucleus histamine levels are maximal and 5‐HT minimal during the dark phase of the illumination cycle. An inverse relationship for these parameters is found during the light phase of the illumination cycle. 4. Pentobarbitone sodium treatment significantly elevates mid‐brain NA and histamine and caudate nucleus histamine levels during the dark phase of the illumination cycle. Although 5‐HT levels are reduced over the entire circadian cycle this change is significant only during the light phase of the illumination cycle. 5. Pentobarbitone sodium treatment reverses the circadian pattern for body temperature, producing a mirror image of the control pattern. 6. The circadian pattern for blood serum histamine levels differs from the C.N.S. pattern for histamine. Peak levels occur at the end of the light phase of the illumination cycle. After pentobarbitone sodium these levels are reduced, although the circadian pattern is similar to the control. 7. Circadian blood glucose patterns have bimodal peaks; a primary peak at the end of the dark phase, a secondary peak at the end of the light phase of the illumination cycle. Pentobarbitone sodium did not significantly alter the pattern. The relationship between this pattern and C.N.S. and peripheral histamine and catechol amines is discussed.

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Section: Discussionmentioning

confidence: 90%

Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium

Friedman¹,

Walker²

1969

The Journal of Physiology

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“…On the other hand, such signs of the behavioral sedation associated with the depression of the tegmental motor response were not observed in the animals that received orphenadrine, atropine or scopolamine . The depression of the head turning reported to be produced by 2.5 mg/kg of chlorpromazine in the cat (10) was also confirmed in the rabbit which received 1 to 2 mg/kg. 2.…”

Section: Effects Of Orphenadrine On the Spontaneous Eegsmentioning

confidence: 65%

“…Such an effect has been utilized for the evaluation of the antiparkinson agents (10,12). In the present experiments the effects of various agents including orphenadrine were ob served on the arousal responses of the cortical EEG and on the motor responses such as the head turning and neck tremor caused by electrical stimulation of the midbrain tegmentum.…”

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confidence: 96%

Comparison of the Electroencephalographic and Motor Effects of Orphenadrine, an Antiparkinson Agent

Ban

Hojo

1968

Japanese Journal of Pharmacology

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Orphenadrine has been reported to improve effectively a variety of skeletal muscle spasms (1-5) and various disorders of parkinsonism (6-9). Orphenadrine is known to be one of anticholinergic agents with weak antihistamine activity (9). The anticholinergic and antihistamine mechanisms seem to be somewhat essential for the antiparkinson drugs (10, 11). The blocking effects of the anticholinergic antiparkinson agents on the reticular ascending function (12) as well as the suppressing effects on the tremor induced either by destructive lesions in the midbrain tegmentum (12) and the reticular formation (14) or by electrical stimulation of these structures (15,16) indicate that the cholinergic mechanism is involved somewhere in the polysynaptic chains of the ascending and descending path ways from the midbrain.These evidences indicate that the suppression of the arousal response in the cortical EEG is predictive for the prevention of the tremor manifestation in the parkinson patients. Such an effect has been utilized for the evaluation of the antiparkinson agents (10, 12). In the present experiments the effects of various agents including orphenadrine were ob served on the arousal responses of the cortical EEG and on the motor responses such as the head turning and neck tremor caused by electrical stimulation of the midbrain tegmentum. However, the uniform and parallel depression of both parameters was not always obtained, varying considerably in effect according to the administered doses and also to the time length after the administration. The antiparkinson characteristics of orphenadrine were discussed, based on the evidences obtained.

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“…Of these agents, the muscarinic agonist oxotremorine (Oxo-T), is unique in producing the typical features of Parkinson's disease (Friedman & Everett, 1964;Jenden, 1968). This effect of Oxo-T is mediated at least in part through a presynaptic cholinergic CH3 dominance at the myoneural junction resulting from activation of presynaptic muscarinic receptors on the motor nerve endings (Das et al, 1978;Ganguly & Das, 1979).…”

Section: Introductionmentioning

confidence: 99%

ANTI‐TREMOR ACTION OF C₁₀DICHOL, A PERIPHERAL ACETYLCHOLINE SYNTHESIS INHIBITOR

Das¹,

Ganguly²,

Vedasiromoni³

1980

British J Pharmacology

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Anti‐tremor action of decamethylene bis‐(hydroxyethly)‐dimethylammonium bromide (C10Dichol), a peripheral acetylcholine synthesis inhibitor, was investigated. C10Dichol inhibited tremor induced by oxotremorine, nicotine and physostigmine and afforded partial protection from physostigmine‐induced mortality in mice. In non‐paralysing doses, C10Dichol antagonized the neuromuscular effects of oxotremorine, nicotine and physostigmine. Prior administration of C10Dichol failed to prevent tremor and neuromuscular paralysis induced by harmine and arecoline. In the absence of any antimuscarinic property of C10Dichol, its neuromuscular effects appeared to be causually related to its anti‐tremor action. This study reveals a possibility for the development of peripherally acting anti‐Parkinson drugs.

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Pharmacological Aspects of Parkinsonism

Cited by 48 publications

References 142 publications

Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium

Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium

Comparison of the Electroencephalographic and Motor Effects of Orphenadrine, an Antiparkinson Agent

ANTI‐TREMOR ACTION OF C₁₀DICHOL, A PERIPHERAL ACETYLCHOLINE SYNTHESIS INHIBITOR

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Pharmacological Aspects of Parkinsonism

Cited by 48 publications

References 142 publications

Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium

Rat brain amines, blood histamine and glucose levels in relationship to circadian changes in sleep induced by pentobarbitone sodium

Comparison of the Electroencephalographic and Motor Effects of Orphenadrine, an Antiparkinson Agent

ANTI‐TREMOR ACTION OF C10DICHOL, A PERIPHERAL ACETYLCHOLINE SYNTHESIS INHIBITOR

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ANTI‐TREMOR ACTION OF C₁₀DICHOL, A PERIPHERAL ACETYLCHOLINE SYNTHESIS INHIBITOR