The production of an alternative laboratory model of the Parkinson syndrome using a new benzylimidoylurea derivative LON 954

Coward, D. M.; Doggett, N.S.

doi:10.1007/bf00439104

Cited by 12 publications

(2 citation statements)

References 27 publications

(23 reference statements)

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“…Bromocriptine relieves the tremor induced in monkeys by lesions of the ventromedial tegmental area of the brainstem (VMT) or in mice by LON 954 (Coward and Doggett 1977). Furthermore, the anti-tremor action of bromocriptine in monkeys is mediated via D2 receptors and is blocked by alpha methyl-p-tyrosine (Lieberman etal.…”

Section: Miscellaneous Motor Behavioursmentioning

confidence: 99%

The motor effects of bromocriptine ? a review

1988

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For many years, bromocriptine has proven to be a useful treatment for some of the disabling motor effects seen in Parkinson's disease. As such, it has been the only commonly used directly acting D2 agonist available. But its mechanism of action has been obscure because many animal models indicated an absolute requirement for the presence of endogenous DA for bromocriptine to have any efficacy, despite its undoubted occupation of the D2 receptor with high affinity. Several scattered reports indicated, however, that bromocriptine could potentiate the effects of a number of other dopamine agonists (such as apomorphine and L-dopa) in a variety of pharmacological models and in the clinic. With the availability of SKF38393 and SCH23390, it soon became clear that bromocriptine, while a selective D2 agonist, depended in an absolute sense on the integrity of the D1 receptors. Thus, if SKF38393 was administered together with bromocriptine to rodents depleted of dopamine, marked locomotor excitation was produced, despite either drug alone being inactive. The present review explores the literature on the motor effects of bromocriptine and endeavours to integrate its behavioural, biochemical and electrophysiological effects into a coherent whole. It closes with a consideration of several remaining unsolved problems associated with the pharmacology of bromocriptine and suggests some future studies.

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Section: Miscellaneous Motor Behavioursmentioning

confidence: 99%

The motor effects of bromocriptine ? a review

1988

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“…Harmine-induced tremor in rats has been proposed to involve an imbalance between the dopaminergic and the 5-HT'ergic function in the central nervous system (Costall et al 1976;Kawanishi et al 1981;Kelly & Naylor 1974;Poirier et al 1968;Sourkes & Poirier 1968). The tremor in-duced by the benzylimidoylurea derivative LON-954 has been suggested to depend on a decreased dopaminergic function in the brain (Coward et al 1977a & b;Coward & Doggett 1977). Iproniazid + 5-HTP induces tremor by probably increasing the 5-HT concentration in the brain as this tremor is inhibited by lysergic acid diethylamide (LSD) (Brimblecombe & Pinder 1972;Yen & Day 1965).…”

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confidence: 99%

Harmine–, LON–954– and 5–Hydroxytryptophan–induced Tremors in Rats Withdrawn from Ethanol

Gothóni

1985

Acta Pharmacologica et Toxicologica

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Abslracl:The tremors induced by harmine, LON-954 (N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride) and 5-hydroxytryptophan (5-HTP) were studied in control rats and in rats withdrawn for 1 W 8 hrs from 6 to 9 days' ethanol administration. The frequencies and the intensities of the tremors were determined electronically. In control rats the frequency spectra of the tremors induced by harmine (20 mg/ kg) and LON-954 (10 mg/kg) showed a narrow peak frequency at about 10 Hz. Atropine (1.2 rng/kg) altered neither the frequency nor the intensity of these tremors. 5-HTP (SO mg/kg) when given 3.5 hrs after iproniazid (100 mg/kg) induced tremor with peak frequencies at 6-7 Hz and 12 Hz. In ethanol-withdrawn rats treated with harmine or LON-954 the frequency analysis of tremor revealed a narrow peak frequency at about 12 Hz, which was neither the characteristic frequency of ethanol withdrawal tremor (6 Hz) nor that of harmine or LON-954 (10 Hz). The intensity of both harmine-and LON-954-induced tremor was significantly increased in ethanol-withdrawn rats. The ethanol-withdrawn rats were markedly sensitized to the effect of iproniazidf 5-HTP, shown by deaths. The peak frequencies of this tremor were the same as those in control rats. The results suggest that harmine-induced tremor involves a dopaminergic-5-HT'ergic imbalance and the tremor induced hy LON-954 a dopaminergic-cholinergic imbalance in the brain. The tremor in ethanol-withdrawn rats seems to he mediated by alterations in the activity of the cerebral 5-HT'ergic system. Key-words:Ethanol withdrawal ~ harmine ~ LON-954 -5-HTPtremorrats. 1 1 3-120. 323, 205-210. 46, 585-589. 6A, 335-346.

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