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Matthew B Weinger - One of the best experts on this subject based on the ideXlab platform.
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pretreatment with sedative hypnotics but not with nondepolarizing Muscle relaxants attenuates alfentanil induced Muscle Rigidity
Journal of Clinical Anesthesia, 1994Co-Authors: Theodore J Sanford, Matthew B Weinger, Ty N Smith, James L BenthuysenAbstract:Abstract Study Objective: To evaluate and compare the efficacy of various pretreatment agents to attenuate or prevent opioid-induced Muscle Rigidity using a well-established, previously described clinical protocol. Design: Prospective, controlled, single-blind, partially randomized study. Setting: Large medical center. Patients: ASA physical status I–III patients undergoing elective surgical procedures of at least 3 hours' duration. Interventions: The effect of pretreatment with nondepolarizing Muscle relaxants (atracurium 40μg/kg or metocurine 50,μg/kg), benzodiazepine agonists (diazepam 5 mg or midazolam 2.5 mg), or thiopental sodium 1 mg/kg on the increased Muscle tone produced by alfentanil 175 ,μg/kg was compared with a control group (given no pretreatment). Measurements and Main Results: Rigidity was assessed quantitatively by measuring the electromyographic activity of five Muscle groups (biceps, intercostals, abdominals, quadriceps, and gastrocnemius). Rigidity also was rated qualitatively by attempts to initiate and maintain mask ventilation, attempts to flex an extremity, and the occurrence of myoclonic movements. Pretreatment with the two nondepolarizing Muscle relaxants had no effect on the severe Muscle Rigidity produced by high-dose alfentanil. Whereas thiopental was only mildly effective, the benzodiazepines midazolam and diazepam significantly attenuated alfentanil Rigidity ( p Conclusion: This study suggests that benzodiazepine pretreatment is frequently, but not always, effective in preventing opioid-induced Muscle Rigidity.
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atipamezole an alpha2 antagonist augments opiate induced Muscle Rigidity in the rat
Pharmacology Biochemistry and Behavior, 1994Co-Authors: Matthew B Weinger, Julie Miriam BednarczykAbstract:Atipamezole is a new, highly selective alpha2-adrenoceptor antagonist currently undergoing clinical trials as an antagonist for dexmedetomidine, a potent alpha2 agonist with sedative and analgesic properties. It has previously been demonstrated that dexmedetomidine, acting at central alpha2 adrenoceptors, antagonizes opiate-induced Muscle Rigidity. However, the role of endogenous alpha2-adrenergic systems in opiate-induced Rigidity remains to be elucidated. The present study was designed to assess the effects of atipamezole on basal Muscle tone and on alfentanil-induced Muscle Rigidity in the rat. Muscle tone was measured using gastrocnemius electromyography (EMG). After a 15-min baseline, saline or atipamezole (0.3 or 1.0 mg/kg) was administered, and 10 min later, saline or alfentanil (50, 150, or 300 micrograms/kg) was injected subcutaneously. Data were collected for an additional 60 min. Atipamezole (1.0 mg/kg) pretreatment (in the absence of alfentanil) produced a small increase in tonic EMG activity when compared with saline pretreatment. After saline pretreatment, significant Muscle Rigidity occurred in the two highest alfentanil dose groups. Atipamezole (0.3 and 1.0 mg/kg) augmented alfentanil-induced Muscle Rigidity. The ability of the alpha2 antagonist to potentiate both basal Muscle tone and alfentanil-induced Rigidity suggests that endogenous adrenergic activity and/or direct alpha2-adrenoceptor interaction with opioid receptors mediate opiate-induced Muscle Rigidity. These findings may be of clinical as well as basic neuropharmacological interest.
Andrzej Pilc - One of the best experts on this subject based on the ideXlab platform.
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mtep a new selective antagonist of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2005Co-Authors: Krystyna Ossowska, S Wolfarth, J Konieczny, Andrzej PilcAbstract:The aim of the present study was to examine a potential antiparkinsonian-like action of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), a new non-competitive antagonist of mGluR5, in the rat models. This compound has affinity for mGluR5 in a nanomolar concentration range and seems to be superior to the earlier known antagonists in terms of its specificity and bioavailability. Catalepsy and Muscle Rigidity induced by haloperidol administered at doses of 0.5 and 1 mg/kg were regarded as models of parkinsonian akinesia and Muscle Rigidity, respectively. MTEP at doses between 0.5 and 3 mg/kg i.p. decreased the haloperidol-induced Muscle Rigidity measured as an increased Muscle resistance of the rat's hind leg in response to passive extension and flexion at the ankle joint. The strongest and the longest effect was observed after the dose of 1 mg/kg. MTEP (0.5-3 mg/kg i.p.) also reduced the haloperidol-induced increase in electromyographic (EMG) activity recorded in the gastrocnemius and tibialis anterior Muscles. MTEP (3 and 5 mg/kg i.p.) inhibited the catalepsy induced by haloperidol. The present study confirms earlier suggestions that the antagonists of mGluR5 may possess antiparkinsonian properties. However, selective mGluR5 antagonists may be more effective in inhibiting parkinsonian Muscle Rigidity than parkinsonian akinesia.
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blockade of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2001Co-Authors: Krystyna Ossowska, J Konieczny, S Wolfarth, Joanna M Wieronska, Andrzej PilcAbstract:The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and Muscle Rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The Muscle Rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior Muscles. MPEP (1.0-10mg/kg ip) inhibited the Muscle Rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the Muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and Muscle Rigidity.
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ly354740 a group ii metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats
Naunyn-schmiedebergs Archives of Pharmacology, 1998Co-Authors: J Konieczny, Krystyna Ossowska, S Wolfarth, Andrzej PilcAbstract:The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like Muscle Rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat’s hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced Muscle Rigidity. The present results suggest that LY354740 counteracts the Muscle Rigidity in an animal model of parkinsonism.
J Konieczny - One of the best experts on this subject based on the ideXlab platform.
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influence of cgs 21680 a selective adenosine a2a agonist on the phencyclidine induced sensorimotor gating deficit and motor behaviour in rats
Psychopharmacology, 2003Co-Authors: Jadwiga Wardas, J Konieczny, M PietraszekAbstract:Rationale Recently it has been suggested that adenosine A2A receptor agonists may be potential antipsychotic drugs. It is, however, not clear whether these compounds may exert their antipsychotic effect without producing extrapyramidal side-effects (e.g. catalepsy, Muscle Rigidity, ataxia). It is known that such side-effects may be due to overactivation of the GABAergic strio-pallidal pathway, which may be estimated as an increased expression of proenkephalin (PENK) mRNA in the striatum.
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blockade of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2001Co-Authors: Krystyna Ossowska, J Konieczny, S Wolfarth, Joanna M Wieronska, Andrzej PilcAbstract:The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and Muscle Rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The Muscle Rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior Muscles. MPEP (1.0-10mg/kg ip) inhibited the Muscle Rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the Muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and Muscle Rigidity.
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sch 58261 an a 2a adenosine receptor antagonist counteracts parkinsonian like Muscle Rigidity in rats
Synapse, 2001Co-Authors: Jadwiga Wardas, J Konieczny, Elzbieta LorenckociAbstract:The aim of the present study was to find out whether blockade of adenosine A(2A) receptors by a selective antagonist, SCH 58261, influenced parkinsonian-like Muscle Rigidity. Muscle tone was examined using a combined mechano- and electromyographic method which simultaneously measured Muscle resistance (MMG) of a rat hindfoot to passive extension and flexion in the ankle joint and electromyographic activity (EMG) of the antagonistic Muscles of that joint: gastrocnemius and tibialis anterior. Muscle Rigidity produced by reserpine (5 mg/kg + alpha-methyl-p-tyrosine, 250 mg/kg) was antagonized by SCH 58261 (0.1-5 mg/kg). SCH 58261 (5 mg/kg) also reduced reserpine-enhanced tonic and reflex EMG activities in both the gastrocnemius and the tibialis Muscles. Moreover, SCH 58261 in doses of 1 and 5 mg/kg abolished Muscle resistance induced by haloperidol (0.5 mg/kg). However, only the highest dose of SCH 58261 (5 mg/kg) decreased tonic EMG activity enhanced by haloperidol. Administration of L-DOPA (75 and 100 mg/kg) dose-dependently decreased the Muscle resistance as well as tonic EMG activity evoked by haloperidol. Combined administration of SCH 58261 (0.1 mg/kg) and L-DOPA (50 mg/kg) in doses which did not affect the haloperidol-induced Muscle Rigidity produced a pronounced synergistic effect. The ability of SCH 58261 to diminish the parkinsonian-like Muscle Rigidity and to potentiate the effect of L-DOPA in this model seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease.
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l 701 324 a selective antagonist at the glycine site of the nmda receptor counteracts haloperidol induced Muscle Rigidity in rats
Psychopharmacology, 1999Co-Authors: J Konieczny, Krystyna Ossowska, G Schulze, H Coper, S WolfarthAbstract:Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like Muscle Rigidity and catalepsy induced by haloperidol in rats. Methods: The Muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior Muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the Muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian Rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.
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ly354740 a group ii metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats
Naunyn-schmiedebergs Archives of Pharmacology, 1998Co-Authors: J Konieczny, Krystyna Ossowska, S Wolfarth, Andrzej PilcAbstract:The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like Muscle Rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat’s hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced Muscle Rigidity. The present results suggest that LY354740 counteracts the Muscle Rigidity in an animal model of parkinsonism.
S Wolfarth - One of the best experts on this subject based on the ideXlab platform.
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mtep a new selective antagonist of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2005Co-Authors: Krystyna Ossowska, S Wolfarth, J Konieczny, Andrzej PilcAbstract:The aim of the present study was to examine a potential antiparkinsonian-like action of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), a new non-competitive antagonist of mGluR5, in the rat models. This compound has affinity for mGluR5 in a nanomolar concentration range and seems to be superior to the earlier known antagonists in terms of its specificity and bioavailability. Catalepsy and Muscle Rigidity induced by haloperidol administered at doses of 0.5 and 1 mg/kg were regarded as models of parkinsonian akinesia and Muscle Rigidity, respectively. MTEP at doses between 0.5 and 3 mg/kg i.p. decreased the haloperidol-induced Muscle Rigidity measured as an increased Muscle resistance of the rat's hind leg in response to passive extension and flexion at the ankle joint. The strongest and the longest effect was observed after the dose of 1 mg/kg. MTEP (0.5-3 mg/kg i.p.) also reduced the haloperidol-induced increase in electromyographic (EMG) activity recorded in the gastrocnemius and tibialis anterior Muscles. MTEP (3 and 5 mg/kg i.p.) inhibited the catalepsy induced by haloperidol. The present study confirms earlier suggestions that the antagonists of mGluR5 may possess antiparkinsonian properties. However, selective mGluR5 antagonists may be more effective in inhibiting parkinsonian Muscle Rigidity than parkinsonian akinesia.
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blockade of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2001Co-Authors: Krystyna Ossowska, J Konieczny, S Wolfarth, Joanna M Wieronska, Andrzej PilcAbstract:The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and Muscle Rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The Muscle Rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior Muscles. MPEP (1.0-10mg/kg ip) inhibited the Muscle Rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the Muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and Muscle Rigidity.
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l 701 324 a selective antagonist at the glycine site of the nmda receptor counteracts haloperidol induced Muscle Rigidity in rats
Psychopharmacology, 1999Co-Authors: J Konieczny, Krystyna Ossowska, G Schulze, H Coper, S WolfarthAbstract:Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like Muscle Rigidity and catalepsy induced by haloperidol in rats. Methods: The Muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior Muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the Muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian Rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.
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ly354740 a group ii metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats
Naunyn-schmiedebergs Archives of Pharmacology, 1998Co-Authors: J Konieczny, Krystyna Ossowska, S Wolfarth, Andrzej PilcAbstract:The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like Muscle Rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat’s hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced Muscle Rigidity. The present results suggest that LY354740 counteracts the Muscle Rigidity in an animal model of parkinsonism.
Krystyna Ossowska - One of the best experts on this subject based on the ideXlab platform.
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mtep a new selective antagonist of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2005Co-Authors: Krystyna Ossowska, S Wolfarth, J Konieczny, Andrzej PilcAbstract:The aim of the present study was to examine a potential antiparkinsonian-like action of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), a new non-competitive antagonist of mGluR5, in the rat models. This compound has affinity for mGluR5 in a nanomolar concentration range and seems to be superior to the earlier known antagonists in terms of its specificity and bioavailability. Catalepsy and Muscle Rigidity induced by haloperidol administered at doses of 0.5 and 1 mg/kg were regarded as models of parkinsonian akinesia and Muscle Rigidity, respectively. MTEP at doses between 0.5 and 3 mg/kg i.p. decreased the haloperidol-induced Muscle Rigidity measured as an increased Muscle resistance of the rat's hind leg in response to passive extension and flexion at the ankle joint. The strongest and the longest effect was observed after the dose of 1 mg/kg. MTEP (0.5-3 mg/kg i.p.) also reduced the haloperidol-induced increase in electromyographic (EMG) activity recorded in the gastrocnemius and tibialis anterior Muscles. MTEP (3 and 5 mg/kg i.p.) inhibited the catalepsy induced by haloperidol. The present study confirms earlier suggestions that the antagonists of mGluR5 may possess antiparkinsonian properties. However, selective mGluR5 antagonists may be more effective in inhibiting parkinsonian Muscle Rigidity than parkinsonian akinesia.
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blockade of the metabotropic glutamate receptor subtype 5 mglur5 produces antiparkinsonian like effects in rats
Neuropharmacology, 2001Co-Authors: Krystyna Ossowska, J Konieczny, S Wolfarth, Joanna M Wieronska, Andrzej PilcAbstract:The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and Muscle Rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The Muscle Rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior Muscles. MPEP (1.0-10mg/kg ip) inhibited the Muscle Rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the Muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and Muscle Rigidity.
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l 701 324 a selective antagonist at the glycine site of the nmda receptor counteracts haloperidol induced Muscle Rigidity in rats
Psychopharmacology, 1999Co-Authors: J Konieczny, Krystyna Ossowska, G Schulze, H Coper, S WolfarthAbstract:Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like Muscle Rigidity and catalepsy induced by haloperidol in rats. Methods: The Muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior Muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the Muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian Rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.
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ly354740 a group ii metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats
Naunyn-schmiedebergs Archives of Pharmacology, 1998Co-Authors: J Konieczny, Krystyna Ossowska, S Wolfarth, Andrzej PilcAbstract:The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like Muscle Rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat’s hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced Muscle Rigidity. The present results suggest that LY354740 counteracts the Muscle Rigidity in an animal model of parkinsonism.
