Effect of idebenone (CV-2619) on memory impairment observed in passive avoidance task in rats with cerebral embolization.
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Effect of idebenone (CV-2619) on memory impairment was studied in rats with cerebral embolization. The cerebral embolization, produced by injecting 2000 microspheres into the internal carotid artery, caused a significant impairment in passive avoidance response. Repeated administrations of idebenone (30 mg/kg/day, i.p.), partially but significantly improved the impairment of the passive avoidance response in the embolized rats. The results suggest that the repeated administration of idebenone exerts an ameliorating effect on memory impairment induced by cerebral embolization. (+info)
Muscarinic acetylcholine receptors in the rabbit ciliary body smooth muscle: spare receptors and threshold phenomenon.
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Interactions of several muscarinic drugs with their receptors were studied in the ciliary body smooth muscles of the rabbit. The ciliary body smooth muscles responded to carbachol, a muscarinic full agonist, with concentration-dependent contractions, and the pD2 value of carbachol was 5.16 +/- 0.05. Atropine, a competitive antagonist of muscarinic receptors, produced a parallel shift to the right in the concentration-response curves for carbachol. Pilocarpine which is a well-known partial agonist on muscarinic receptors in most smooth muscles did not cause any contraction in this tissue. The drug, however, behaved as a competitive antagonist on the muscarinic receptors in the ciliary body smooth muscles. The pA2 values of atropine and pilocarpine versus carbachol obtained from the Schild plot are 8.97 +/- 0.25 and 5.17 +/- 0.09, respectively. On the other hand, arecoline and oxotremorine acted as a partial agonist in this tissue. The intrinsic activity, and pD2 and pA2 values were 0.41 +/- 0.02, 4.93 +/- 0.05 and 5.32 +/- 0.05 for arecoline respectively, and were 0.26 +/- 0.02, 5.64 +/- 0.08 and 6.12 +/- 0.16 for oxotremorine, respectively. The pA2 values of these drugs were significantly larger than the corresponding pD2 values of the drugs. The values of the negative log molar dissociation constant of carbachol, arecoline and oxotremorine estimated by the method of partial irreversible blockade of spare receptors with 3 X 10(-6) M phenoxybenzamine were 4.53 +/- 0.08, 5.20 +/- 0.09 and 6.02 +/- 0.06, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Effects of cholinergic drugs on aversive operant behavior induced by dorsal central gray stimulation in rats.
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Involvement of a central cholinergic mechanism in the central aversive operant behavior induced by dorsal central gray (DCG) stimulation was investigated in rats. Each animal was chronically implanted with bipolar electrodes at the DCG and was trained to press a lever to decrease the DCG-stimulation current. Physostigmine (0.1 and 0.2 mg/kg, i.p.) and arecholine (0.5-2.0 mg/kg, i.p.) produced an increase of DCG-stimulation threshold at 0.5-2 hr and 1-4 hr, respectively, after the administration. On the other hand, scopolamine (0.1-0.5 mg/kg, i.p.) and atropine (5 and 10 mg/kg, i.p.) caused a marked decrease of the threshold at 0.5-2 hr after. In addition, an increasing effect of physostigmine on the threshold was decreased by scopolamine. Physostigmine potentiated the increasing effect of chlorimipramine on the stimulation threshold, while scopolamine suppressed it. These results suggest that the operant behavior induced by DCG-stimulation may be related to not only the central serotonergic mechanism but also to the cholinergic mechanism. (+info)
Muscarinic cholinergic binding in rat brain.
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Binding sites with high affinity and specificity for [(3)H]quinuclidinyl benzilate (QNB) are present in homogenates of rat brain. The characteristics of the binding sites resemble those of muscarinic cholinergic receptors. Specific binding is saturable with respect to [(3)H]QNB and tissue concentration and is time-, temperature-, and pH-dependent. The bimolecular rate of association (2.0 x 10(8) M(-1) min(-1)) and dissociation (1.2 x 10(-2) min(-1)) at 35 degrees indicate a dissociation constant of 60 pM and a density of 65 pmol/g of brain. Muscarinic antagonists and agonists displace specific [(3)H]QNB binding, while nicotinic and non-cholinergic drugs possess little affinity for [(3)H]QNB-binding sites. (+info)
Effects of some sympathomimetic drugs and their antagonists on afterdischarges elicited in chronically isolated slabs of cerebral cortex.
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1. The role of sympathomimetic agents in the maintenance and termination of induced cortical epileptiform activity was studied in chronically neuronally isolated slabs of cerebral cortex in the suprasylvian gyrus of unanaesthetized, unrestrained cats.2. The administration of the sympathomimetic agents (+)-amphetamine, methamphetamine, tyramine, and ephedrine resulted in a highly significant decrease in the duration of epileptiform afterdischarge (EADs).3. The alpha-adrenoceptor blocking drugs phenoxybenzamine, phentolamine and tolazoline did not significantly alter the duration of EADs but prevented the decrease in duration of EADs produced by the sympathomimetic drugs.4. The effect of atropine and arecoline on the duration of EADs, previously described, were not modified by the alpha-adrenoceptor blocking drugs, but atropine prevented and reversed the inhibitory action of amphetamine.5. It is suggested that (1) in the chronically neuronally isolated cortical slab there is normally no spontaneous adrenergic activity, (2) a cortical, cholinergic inhibitory mechanism, previously described, is modulated by ascending adrenergic influences, (3) adrenergic cholinergic linkages might be arranged in the cortex in an alternating network, as proposed by Feldberg. (+info)
Surveillance of Echinococcus granulosus in dogs with arecoline hydrobromide.
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Arecoline hydrobromide has been used for almost half a century for the treatment of Echinococcus granulosus in dogs. Trials in New Zealand showed that it had real limitations for this purpose. Its main value lies in its use as a diagnostic agent for detecting infections in dogs on a group basis. The data so obtained can be used in educating dog owners as well as for providing base-line data and an index of progress in a continuing control programme. The drug's limitations for treatment and value as a diagnostic agent in a field trial are assessed. (+info)
Subsensitivity to cholinoceptor stimulation of the human iris sphincter in situ following acute and chronic administration of cholinomimetic miotic drugs.
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1 Maximal pupillary miosis was obtained with single topical applications of 4 cholinomimetic drugs in therapeutic concentrations to normal human subjects. 2 When the pupil had recovered from the miosis, there remained a reduced light reflex response of 22.7% at 24 h after aceclidine, 18.0% at 31 h after pilocarpine, 10.3% at 48 h after physostigmine and 4.9% at 7 h after arecoline. 3 This reduced sensitivity to light was accompanied by an overshoot of the resting pupil diameter and, after aceclidine miosis, a reduced response to a second application of miotic. 4 Similar findings were observed in glaucoma patients following withdrawal of chronic pilocarpine therapy. 5 It is suggested that the slowly reversible after-effects of acute and chronic administration of cholinomimetic miotics can be explained by desensitization of iris sphincter cholinoceptors. (+info)
Impaired autonomic responsiveness of the cardiovascular system of the rat induced by a heat-labile component of Bordetella pertussis vaccine.
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Bordetella pertussis vaccination induces severe impairment of the autonomic responsiveness of the cardiovascular system in rats. The vasodilation after beta 2-adrenoceptor stimulation with salbutamol as well as the negative chronotropic action induced by the muscarinic receptor stimulant arecoline were inhibited 4 days after vaccination. Moreover, basal blood pressure values appeared to be significantly lower in B. pertussis-vaccinated rats compared with control animals. These effects were dependent upon the bacterial strain used. Differences in pharmacological activity due to strain differences paralleled variations in the content of lymphocytosis-promoting factor of the vaccine. The inhibitory effects were absent after the administration of vaccine heated for 1 h at 80 degrees C, implicating an important role for a heat-labile component, e.g., lymphocytosis-promoting factor, and not for a heat-stable constituent, e.g., endotoxin (lipopolysaccharide). Previous studies indicate that some early biological effects elicited by B. pertussis vaccine can be attributed to lipopolysaccharide, whereas late induced effects are mainly brought about by lymphocytosis-promoting factor. For that reason a role for lipopolysaccharide might be excluded because 5 h after vaccination no disturbances of the autonomic nervous system were observed. We conclude that B. pertussis vaccination induces autonomic hyporesponsiveness due to a heat-labile component that is assumed to be lymphocytosis-promoting factor. (+info)