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  • 1
    Electronic Resource
    Electronic Resource
    THE EFFECT OF APOMORPHINE AND CLONIDINE ON LOCOMOTOR ACTIVITY IN MICE AFTER LONG TERM TREATMENT WITH HALOPERIDOL (1977)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 4 (1977), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Mice were given haloperidol (approximately 3 mg.kg−1 day−1) or vehicle for 21 days and then withdrawn from the drug. All tests were performed 4 days after withdrawal.2. Haloperidol treated mice (premedicated with reserpine plus a-methyl-p-tyrosine) displayed an increased locomotor response to apomorphine and to apomorphine plus clonidine, but neither haloperidol- or vehicle-treated animals revealed any stimulant response to clonidine.3. In mice which had not been pretreated with reserpine plus a-methyl-p-tyrosine, clonidine produced a significant stimulation of locomotor activity in animals withdrawn from haloperidol but not in those withdrawn from the vehicle. Phen-oxybenzamine blocked the locomotor stimulant difference between these two groups, but did not completely antagonize the stimulant effect of clonidine in mice withdrawn from haloperidol. Pimozide was largely effective in blocking the clonidine-induced stimulation. Co-administration of phenoxybenzamine and pimozide was completely effective in blocking the stimulant effect of clonidine in mice withdrawn from haloperidol.4. The evidence for a change in catecholamine receptor sensitivity was supported by the increased stimulant effect of dexamphetamine in the haloperidol-treated, compared to the vehicle-treated animals.5. The data suggest that there is a change in the functional responsiveness of both adrenergic and dopaminergic receptors after withdrawal from long term haloperidol treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1977.tb02613.x
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  • 2
    Electronic Resource
    Electronic Resource
    The hyperkinetic syndrome following long-term haloperidol treatment: Involvement of dopamine and noradrenaline (1979)
    Springer
    Journal of neural transmission 44 (1979), S. 175-186 
    Details
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice withdrawn for 7 days from a 35-day treatment period with haloperidol (3 mg/kg/day) displayed significantly greater spontaneous locomotor activity (hyperkinesia) than animals withdrawn from the vehicle. The hyperkinesia was antagonized by phenoxybenzamine (anα-adrenergic receptor antagonist) and by FLA-63 (a dopamine-β-hydroxylase inhibitor) but not by haloperidol (a dopamine receptor antagonist).α-Methyl tyrosine (a tyrosine hydroxylase inhibitor) was effective in antagonizing the hyperkinesia and this blockade byα-methyl tyrosine could be completely reversed by the administration of a low dose of the catecholamine precursor, DOPA. The data suggest that noradrenergic systems are of importance for the manifestation of the hyperkinetic syndrome seen in mice withdrawn from long-term haloperidol treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01253061
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  • 3
    Electronic Resource
    Electronic Resource
    Long-term haloperidol-treatment of mice: A change in β-adrenergic receptor responsiveness (1979)
    Springer
    Journal of neural transmission 44 (1979), S. 187-195 
    Details
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice administered haloperidol 3 mg/kg/day in their drinking water for 21 days were tested for their locomotor responsiveness to saline or acid vehicle,dl-, l- ord-propranolol, metoprolol, butoxamine or practolol. Haloperidol-treated animals administered saline or acid-vehicle were, in five of six experiments, more active than animals withdrawn from vehicletreatment. Haloperidol- and vehicle-treated animals responded differently to the non-selectiveβ-adrenoreceptor antagonists (dl-propranolol andl-propranolol) and selectiveβ 1-adrenoreceptor antagonists (practolol and metoprolol), but not to a selectiveβ 2-adrenoreceptor antagonist (butoxamine). Withdl-propranolol (4 mg/kg) the locomotor activity of halo-peridol-treated animals was significantly (0.01〈P〈0.02) greater than that of the vehicle-treated animals. Similar effects in the same direction were seen withl-propranolol (1 mg/kg, 0.005〈P〈0.01), practolol (10 and 100 mg/kg, 0.025〈P〈0.05 and 0.01〈P〈0.025 respectively) and metoprolol (8 mg/kg, 0.005〈P〈0.01). Thed-isomer of propranolol which is about 50 times less active as aβ-adrenoreceptor antagonist than thel-isomer, although having equal membrane stabilizing effects, did not differentially affect haloperidol- or vehicle-treated groups. The results suggest that there has been a change inβ 1-adrenoreceptor responsiveness in animals withdrawn from long-term haloperidol treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01253062
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  • 4
    Electronic Resource
    Electronic Resource
    The demonstration of a change in responsiveness of mice to physostigmine and atropine after withdrawal from long-term haloperidol pretreatment (1977)
    Springer
    Journal of neural transmission 40 (1977), S. 181-189 
    Details
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice, administered haloperidol 3 mg/kg/day, in their drinking water for 21 days, were tested for their responsiveness to cholinergic and anticholinergic drugs 4 days after withdrawal from haloperidol (or vehicle). Haloperidol-treated animals administered methylhyoscine (1 mg/kg i.p.) and various doses of physostigmine (5 to 1215μg/kg) displayed significantly less depression of locomotor activity than vehicle-treated animals. Atropine, 5 mg/kg, whilst ineffective in producing locomotor stimulation in vehicle-treated animals, produced marked stimulation in haloperidol-treated animals. Methylatropine (5 mg/kg) did not produce significant stimulation in either group. Dopamine receptor supersensitivity was present in these animals as haloperidol-treated mice, pretreated withα-methyl-tyrosine and reserpine, displayed a significantly greater locomotor response to apomorphine than did vehicle-treated animals. The data support the hypothesis that long-term administration of haloperidol produces an apparent hyposensitivity of central muscarinic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01300132
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  • 5
    Electronic Resource
    Electronic Resource
    Invited commentary (1978)
    Springer
    World journal of surgery 2 (1978), S. 173-174 
    Details
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01553543
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  • 6
    Electronic Resource
    Electronic Resource
    Long-term l-Dopa pretreatment of mice: Central receptor subsensitivity or supersensitivity? (1979)
    Springer
    Psychopharmacology 66 (1979), S. 55-61 
    Details
    ISSN: 1432-2072
    Keywords: l-Dopa ; Chronic ; Apomorphine ; Dexamphetamine ; Subsensitivity ; Supersensitivity ; Dopamine ; Noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of acute and repeated treatments with l-Dopa in oral doses of 200 mg/kg plus benserazide (50 mg/kg) was studied using locomotor activity in mice as a model of central catecholaminergic function. Mice pretreated with l-Dopa once daily for 1, 4 or 10 days responded to a challenge dose of l-Dopa (same dose as above) 1 day later with a more pronounced increase in motor activity than vehiclepretreated animals. Dexamphetamine-induced (0.5, 1.0 or 2.0 mg/kg) stimulation was found not to be significantly different in the two pretreatment groups when mice were challenged 1 day after one or four pretreatment doses of l-Dopa. However, a reduced response to dexamphetamine was observed in l-Dopa-pretreated mice (compared to vehicle-treated mice) on withdrawal of the mice from a 10-day l-Dopa pretreatment schedule. One day after one l-Dopa dose, with or without premedication with α-methyl-p-tyrosine (200 mg/kg) plus reserpine (10 mg/kg), mice responded to apomorphine (1.0 mg/kg) with significantly less activity than vehicle-pretreated mice. In contrast, 1 day after ten doses of l-Dopa, there was a shift to the left of the dose-response curve to apomorphine, which did not, however, occur 4 days after withdrawal. Hence, marked dopamine receptor sensitivity changes seem not to be of primary importance for l-Dopa hyperactivity in l-Dopa-pretreated mice. The present study also suggests that dopaminergic changes are not of consequence in the activity induced by dexamphetamine in l-Dopa-pretreated animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431990
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  • 7
    Electronic Resource
    Electronic Resource
    Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse (1979)
    Springer
    Psychopharmacology 61 (1979), S. 281-285 
    Details
    ISSN: 1432-2072
    Keywords: Writhing ; Δ 9-Tetrahydrocannabinol ; Cannabidiol ; Abdominal constriction ; Drug interactions ; Cannabinol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of Δ 9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8α,11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E1 (PGE1) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED50 in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED50 range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE1 as the nociceptive agent, 11-OH THC was equipotent to THC while 8α,11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432273
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  • 8
    Electronic Resource
    Electronic Resource
    The effect of cannabidiol, alone and in combination with ethanol, on human performance (1979)
    Springer
    Psychopharmacology 64 (1979), S. 243-246 
    Details
    ISSN: 1432-2072
    Keywords: Cannabidiol ; Ethanol ; Human ; Performance ; Cognitive ; Perceptual ; Motor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifteen volunteers received cannabidiol (CBD) (320 μg/kg) or placebo (both orally, T0), and 60 min later they consumed an ethanolic beverage (0.54 g/kg) or placebo. The effects were measured at T1 (100 min after CBD ingestion), T2 (160 min) and T3 (220 min) using cognitive, perceptual and motor function tests. Factorial analysis indicated that test procedures could be adequately expressed by three rotated factors: A reaction speed factor (I), a standing steadiness factor (II) and a psychomotor coordination/cognitive factor (III). Ethanol produced a significant decrement in factor III. There was no demonstrable effect of CBD, either alone or in combination with ethanol. Neither CBD nor ethanol produced any significant effect on pulse rate. Prior administration of CBD did not significantly affect the blood ethanol levels. Whilst the subjects were able to identify correctly when they were given ethanol, they did not report any subjective effects of CBD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00496070
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  • 9
    Electronic Resource
    Electronic Resource
    A pharmacological study of changes in central nervous system receptor responsiveness after long-term dexamphetamine and apomorphine administration (1978)
    Springer
    Psychopharmacology 56 (1978), S. 317-326 
    Details
    ISSN: 1432-2072
    Keywords: Amphetamine ; Apomorphine ; Chronic treatment ; Dopamine ; Locomotor activity ; Noradrenaline ; Supersensitive receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mice administered dexamphetamine (4 mg/kg i.p.) once daily for 20 days displayed an enhanced locomotor response (compared to that of vehicletreated mice) to dexamphetamine when challenged 4 to 16 days but not when challenged 32 days after withdrawal. In the experiments described a 20-day dexamphetamine administration followed by an 8-day withdrawal period was used. Pimozide or haloperidol not only completely antagonised the enhanced response to dexamphetamine (2 mg/kg i.p.) in dexamphetamine-treated mice, but also antagonised all dexamphetamine-induced stimulation. Reserpine, in contrast, preferentially blocked the difference in the response to dexamphetamine of dexamphetamine-and vehicle-treated mice, without antagonising all the dexamphetamine-induced locomotion. The stimulation produced in dexamphetamine-(but not in vehicle-) treated mice by dexamphetamine was partially blocked by phentolamine, phenoxybenzamine, and propranolol. FLA-63 did not significantly influence the response to dexamphetamine in either group. That a dopaminergic mechanism plays a major role in the enhanced response to dexamphetamine was shown by the significantly greater response in dexamphetamine-treated mice to apomorphine challenge. The treatment of mice with apomorphine (10 mg/kg/day i.p. for 20 days), produced a greater response to apomorphine challenge in the apomorphine-treated mice than in vehicle-treated mice 8 days after withdrawal. The data show that with long-term administration both dexamphetamine and apomorphine are able to produce in mice what appear to be supersensitive dopamine receptors. Moreover, the enhanced response to dexamphetamine after withdrawal from long-term dexamphetamine treatment appears to require the presence of reserpine-sensitive amine stores and, to a lesser extent, the presence of unblocked α-adrenergic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432856
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  • 10
    Electronic Resource
    Electronic Resource
    New orally effective chromone derivatives for the treatment of asthma (1977)
    Springer
    Inflammation research 7 (1977), S. 443-445 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two new chromone derivatives have been identified which possess oral anti-allergic activity in the rat PCA model of immediate hypersensitivity. They may have a wider spectrum of anti-allergic activity than disodium cromoglycate (SCG) since they are effective in in vitro tests involving sensitized basophils, in which SCG is inactive. Both compounds, when given orally, provide relief from experimental and clinical asthma in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01966850
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