Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Sep 2011
Comparative StudyOral tremor induced by galantamine in rats: a model of the parkinsonian side effects of cholinomimetics used to treat Alzheimer's disease.
Anticholinesterases are the most common treatment for Alzheimer's disease, and, in recent years, a new group of cholinesterase inhibitors (i.e. rivastigmine, galantamine, and donepezil) has become available. Although these drugs improve cognitive symptoms, they also can induce or exacerbate parkinsonian symptoms, including tremor. The present studies were conducted to determine if galantamine induces tremulous jaw movements, a rodent model of parkinsonian tremor, and to investigate whether these oral motor impairments can be reversed by co-administration of adenosine A(2A) antagonists. ⋯ P.) produced a dose dependent suppression of tremulous jaw movements induced by a 3.0 mg/kg dose of galantamine, indicating that galantamine induces these tremulous oral movements through actions on muscarinic acetylcholine receptors. In two additional studies, analyses of freeze-frame video and electromyographic activity recorded from the lateral temporalis muscle indicated that the local frequency of these galantamine-induced jaw movements occurs in the 3-7 Hz frequency range that is characteristic of parkinsonian tremor. In the final experiment, the adenosine A(2A) antagonist MSX-3 significantly attenuated the tremulous jaw movements induced by the 3.0mg/kg dose of galantamine, which is consistent with the hypothesis that co-administration of adenosine A(2A) antagonists may be beneficial in reducing parkinsonian motor impairments induced by anticholinesterase treatment.
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Pharmacol. Biochem. Behav. · Sep 2011
Comparative StudySubeffective doses of nitroparacetamol (NCX-701) enhance the antinociceptive activity of the α₂-adrenoceptor agonist medetomidine.
The α₂-adrenergic system is involved in pain processing and inflammation-induced sensitization. α₂-adrenoceptor agonists induce analgesia, and this effect is greater when administered in combination with other analgesics. In the present study, we assessed a possible enhancement of antinociception combining the α₂-adrenoceptor agonist medetomidine with subeffective doses of NCX701 (nitroparacetamol). ⋯ In addition, the duration of antinociception was significantly longer (P<0.001, 100 min after administration). The use of low doses of NCX701 and α₂-adrenoceptor agonists might open new perspectives in the treatment of inflammatory pain.
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Pharmacol. Biochem. Behav. · Sep 2011
Comparative StudyPharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats.
The present study investigates the interaction of curcumin with four antiepileptic drugs (AEDs) in male Wistar rats. In the first protocol, seizures were induced using pentylenetetrazole (PTZ) and valproate was injected intraperitoneally (i.p.) in therapeutic and sub-therapeutic doses 30min before PTZ administration. Curcumin was co-administered with sub-therapeutic dose of valproate 60min before PTZ injection. ⋯ Additionally, curcumin reversed the oxidative stress due to seizures. However, curcumin co-administration did not cause any significant alteration in the serum levels of the AEDs. The results thus suggest the potential of curcumin as an adjunct to these AEDs in epilepsy with the advantage of increasing the efficacy, reducing the dose and side effects of the AEDs.
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Pharmacol. Biochem. Behav. · Jul 2011
Comparative StudyBlockade of the antinociception induced by diclofenac, but not of indomethacin, by sulfonylureas and biguanides.
There is evidence that administration of sulfonylureas, such as glibenclamide and tolbutamide, blocks diclofenac-induced antinociception, suggesting that diclofenac activates ATP-sensitive K(+) channels. However, there is no evidence for the interaction between diclofenac and other hypoglycemic drugs, such as the biguanides metformin or phenformin. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, as well as two biguanides, metformin and phenformin, have any effect on the systemic antinociception that is induced by diclofenac and indomethacin using the rat formalin test as an animal model. ⋯ Systemic pretreatment with glibenclamide (3 and 10mg/kg), glipizide (3 and 10mg/kg), metformin (100 and 180mg/kg) or phenformin (100 and 180mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P<0.05). In contrast, pretreatment with glibenclamide, glipizide, metformin or phenformin did not block indomethacin-induced systemic antinociception (P>0.05). These data suggest that diclofenac, but not indomethacin, activated K(+) channels and metformin and phenformin-dependent mechanisms, which resulted in systemic antinociceptive effects in the rat formalin test.
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Pharmacol. Biochem. Behav. · Jun 2011
Pharmacological characterization of AM1710, a putative cannabinoid CB2 agonist from the cannabilactone class: antinociception without central nervous system side-effects.
Cannabinoid CB(2) agonists produce antinociception without central nervous system (CNS) side-effects. This study was designed to characterize the pharmacological and antinociceptive profile of AM1710, a CB(2) agonist from the cannabilactone class of cannabinoids. AM1710 did not exhibit off-target activity at 63 sites evaluated. ⋯ In conclusion, AM1710, a CB(2)-preferring cannabilactone, produced antinociception in the absence of CNS side-effects. Thus, any CB(1)-mediated antinociceptive effects of this compound may be attributable to peripheral CB(1) activity. The observed pattern of pharmacological specificity produced by AM1710 is consistent with limited blood brain barrier penetration of this compound and absence of CNS side-effects.