Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

.1 mol/L CaCl2 0.5 microliters, 0.06 mol/L ACh 0.5 microliters, 5.4 x 10(-3) mol/L gallamine triethiodide (cholinergic nicotinic receptor blocker) 0.5 microliter and 14.4 x 10(-3) mol/L atropine (cholinergic muscarinic receptor blocker) 0.5 microliter were injected through bilateral intracranial cannulae in rat habenula. Pain threshold was measured by the latency of tail-flick reflex elicited by radiant heat exposure before and after intracerebral injection. CaCl2 significantly reduced the basic pain threshold and weakened the effect of the acupuncture analgesia. ACh apparently antagonized the effect of acupuncture analgesia. Gallamine triethiodide could recover the pain threshold almost to the raised level by acupuncture, but atropine only strengthened the effect on pain threshold weakly and briefly. The results suggest that the antagonistic effect of Ca2+ may be mediated via ACh in habenula.
 ...
PMID:[Antagonistic effect of electro-acupuncture analgesia with Ca2+ injection into habenula could be reversed by gallamine triethiodide]. 129 45

After rats received electroacupuncture (EA), leucine-enkephalin (LEK) content in striatum and dopamine (DA) concentration in both brain stem and diencephalon markedly increased, and noradrenaline (NA) level in telencephalon definitely decreased with an obvious elevation of pain threshold. However, a previous intraperitoneal injection of atropine, a blocker of muscarinic receptor, not only partially blocked the analgesic effect of EA, but also changed the effects of EA on LEK, NA and DA contents of the brain. The results indicate that cholinergic system plays an important role in electroacupuncture analgesia (EAA), which may be fulfilled partially through the central LEK and catecholamine (CA) systems.
 ...
PMID:Effects of atropine on the changes of pain threshold and contents of leucine-enkephalin and catecholamines of the brain in rats induced by EA. 149 39

Clinically relevant aspects of the muscarinic transmission in the CNS are mentioned. This transmission depends on the action of acetylcholine (ACh) on the muscarinic receptor and has been better elucidated than the CNS-cholinergic transmission subserved by the nicotinic receptor. Sub-types of the muscarinic receptor have been demonstrated. They are involved in many functions of the CNS. Therefore, disturbance of the CNS muscarinic transmission by ACh-antagonists or lack of ACh results in a colorful but unpredictable behavioural syndrome which is known as the central anticholinergic syndrome (CAS). To a certain degree, the CAS follows all forms of general anaesthesia. It can be prevented or treated by physostigmine which can elevate ACh-levels in the CNS. Postoperative restitution of the CNS-muscarinic transmission results in appropriate behavioural functioning early recovery. Normalization of ACh in the CNS also enhances analgesia and helps to sustain adequate breathing, heart rate and cardiovascular tone.
 ...
PMID:The central muscarinic transmission during anaesthesia and recovery--the central anticholinergic syndrome. 165 14

Intrathecally administered alpha 2-adrenergic agonists produce analgesia in humans but may also produce hypotension and bradycardia. To further characterize hemodynamic depression produced by intrathecally administered alpha 2-adrenergic agonists, clonidine (100-1,500 micrograms) was injected into the cervical, thoracic, or lumbar intrathecal space of conscious sheep. Only thoracic intrathecal clonidine injection (100 or 300 micrograms) decreased blood pressure, whereas these doses did not affect blood pressure when injected at other sites. A greater clonidine dose (1,500 micrograms) increased blood pressure to a similar degree at all sites. Hypotension after thoracic intrathecal clonidine injection was inhibited by pretreatment with the alpha 2-adrenergic antagonist idazoxan (1 mg, intrathecally) or the depleter of acetylcholine stores hemicholinium-3 (2 mg, intrathecally), suggesting an action at alpha 2-adrenoceptors on cholinergic preganglionic sympathetic neurons. ST-91, a polar clonidine analog, did not decrease blood pressure after thoracic intrathecal injection. Intrathecal injection of the muscarinic receptor agonist carbamylcholine increased blood pressure. These data describe a complex action of intrathecal alpha 2-adrenergic agonists on hemodynamic parameters that is dependent on site of injection, drug dose, and drug lipophilicity; that can be explained by anatomic factors; and that may possibly be exploited to minimize hemodynamic depression from these agents.
 ...
PMID:Site of hemodynamic effects of intrathecal alpha 2-adrenergic agonists. 192 92

1. The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot-plate, writhing and tail-flick tests. 2. Atropine dose-dependently produced analgesia, no effect and hyperalgesia. Analgesia was observed in both species with doses ranging from 1 to 100 micrograms kg-1 while hyperalgesia was obtained with 5 mg kg-1. 3. Atropine antinociception was prevented by pirenzepine (0.1 microgram per mouse, i.c.v.), dicyclomine (10 mg kg-1, i.p.), atropine-methylbromide (0.5 microgram per mouse, i.c.v.) and hemicholinium-3 (1 microgram per mouse, i.c.v.). Naloxone (1 mg kg-1, i.p.), alpha-methyl-p-tyrosine (100 mg kg-1, s.c.) and reserpine (2 mg kg-1, i.p.) were ineffective. 4. The site of atropine analgesia is in the CNS since it exerts its antinociceptive effect also when injected i.c.v. (1-10 ng per mouse). Moreover drugs which do not cross the blood-brain barrier, such as hemicholinium-3, pirenzepine and atropine methylbromide, were unable to antagonize atropine analgesia if administered i.p. 5. Atropine also in vitro, showed a biphasic action on electrically-evoked guinea-pig ileum contractions. Concentrations between 10(-14) and 10(-12) M increased electrically and nicotine-evoked contractions but did not affect acetylcholine- and oxotremorine-evoked contractions. Concentrations above 10(-9) M inhibited both electrically- and drug (acetylcholine, nicotine and oxotremorine)-evoked contractions while they were ineffective on unstimulated ileum. 6. On the basis of the above findings, amplification of cholinergic transmission by very low doses of atropine is postulated, through a selective blockade of presynaptic muscarinic autoreceptors, as the likely mechanism of action. 7. Atropine antinociception, unlike oxotremorine antinociception, was obtained without any impairment of mouse rota-rod performance. 8. The antagonism by pirenzepine and dicyclomine of oxotremorine and atropine antinociception suggests that M1 muscarinic receptor subtypes are responsible for cholinergic analgesia.
 ...
PMID:Investigation into atropine-induced antinociception. 228 66

The antinociceptive effect of intrathecally administered carbachol at the L1/L2 level in the rat was evaluated using the tail immersion test. A dose dependent increase in the nociceptive reaction times was evident following intrathecal carbachol in the dose range of 2.5-15 micrograms. At doses of 20 micrograms and above, although still effective in the test, motor impairment was pronounced. The antinociception was antagonized with atropine, and with either pirenzepine (PZ) or AFDX 116, which are selective M1 and M2 muscarinic receptor blocking drugs, respectively. Spinal cholinergic pain modulation was also studied in rats pretreated with DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), which causes a selective depletion of the noradrenergic nerve fibres in the CNS. The increased latency times after spinal carbachol were attenuated in animals depleted of spinal noradrenaline by DSP4. In conclusion, spinal analgesia by carbachol in the rat may therefore be mediated through both M1 and M2 muscarinic receptor stimulation in the spinal cord. It is also concluded that this spinal cholinergic pain modulation is interacting with spinal noradrenergic nerve terminals, but that the mechanism of the interaction remains to be established.
 ...
PMID:Characterization of the antinociception induced by intrathecally administered carbachol. 274 39

The effects of the muscarinic receptor antagonist scopolamine upon analgesia induced by D-ala-D-leu-enkephalin (DADL), beta-endorphin (BEND) and morphine were examined. While scopolamine (10 mg/kg, IP) significantly potentiated the analgesic responses following DADL (40 micrograms, ICV) and morphine (5 mg/kg, SC) on the jump test, it failed to alter significantly BEND (1 microgram, ICV) analgesia.
 ...
PMID:Selective potentiations in opioid analgesia following scopolamine pretreatment. 294 16

In order to study the ontogenesis of cholinergically mediated analgesia in the central nervous system (CNS), 10-day-, 28-day-, and 3-month-old rats were injected with .025, .05, and .10 mg/kg of oxotremorine, a muscarinic receptor agonist. To restrict the effect of oxotremorine to the CNS, methylscopolamine, a peripheral muscarinic antagonist, was injected simultaneously (.19 mg/kg, a dose equimolar to .10 mg/kg of oxotremorine). Following drug injections the tail-flick procedure was used to assess analgesia. Results revealed that oxotremorine was completely ineffective in producing analgesia in the 10-day- and 28-day-old age groups. By 3 months of age oxotremorine produced a dose-dependent analgesia. Since most neurochemical markers of cholinergic receptor function are at mature or near mature levels by 28 days of age, neurochemical indexes of receptor function overestimate the analgesic function of the central cholinergic system.
 ...
PMID:Developmental differences in the analgesia produced by the central cholinergic system. 359 60

The present study assessed in rats the effects of muscarinic receptor antagonism upon analgesia induced by cold-water swims (CWS: 2 degrees C for 3.5 min) and 2-deoxy-D-glucose (2DG: 600 mg/kg). First, CWS analgesia was significantly reduced 30 min after the swim by scopolamine (0.01 and 0.1 mg/kg) and methylscopolamine (10 mg/kg) pretreatment, and was eliminated 60 min after the swim by scopolamine (0.01-10 mg/kg) and methylscopolamine (1,10 mg/kg) pretreatment. In contrast, scopolamine potentiated CWS hypothermia. Second, while scopolamine (1 mg/kg) and methylscopolamine (1,10 mg/kg) pretreatment prolonged 2DG analgesia, both antagonists dose-dependently reduced 2DG hyperphagia. Third, the changes in analgesic and hypothermic stress responses were not due to baseline shifts in jump thresholds or body temperatures. However the dose-dependent reductions by scopolamine and methylscopolamine in baseline food intake and 2DG hyperphagia were significantly correlated. Fourth, the dose-dependent reduction by scopolamine and methylscopolamine of pilocarpine analgesia differed in pattern from the other analgesic effects, suggesting heterogeneity in muscarinic receptor modulation of different analgesic responses.
 ...
PMID:Effects of muscarinic receptor antagonism upon two forms of stress-induced analgesia. 374 24

The present work is an attempt to elucidate: (1) whether highly rigid structural analogs of acetylcholine are still capable of activating the muscarinic receptor; (2) whether such analogs, be they agonists or antagonists, discriminate among the various ACh-mediated functions, thereby providing a tool for the study of a possible receptor heterogeneity; (3) whether structural rigidity is a significant factor in the kinetics of drug-receptor interaction. To this end, we investigated some properties of drugs in the spiro-(1,3-dioxolane-4,3')-quinuclidine system (SDQ) which embodies the muscarinic pharmacophore in a framework of utmost rigidity. Wherever possible, these properties were compared with those of a closely related but more flexible analog. Variation in effect between members of a rigid-flexible pair or among drugs of varying rigidity is considered to reflect varying affinities towards various sites of action. 2-Methyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-30) is a weak but selective muscarinic agonist. It can be viewed as a highly rigid version of 3-acetoxyquinuclidine (3-AcQ) and it can be used as a probe for detection of heterogeneity among muscarinic receptors. AF-30 is equipotent with 3-AcQ in causing tremors (mice), but has 1/17th the activity of 3-AcQ in the guinea-pig ileum, 1/30th in lowering blood pressure (cats) and 1/10th in inducing analgesia (mice). 2-Diphenylmethyl-spiro(1,3-dioxolane-4',3)-quinuclidine (AF-41) and 2.2-diphenyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-32 are potent antagonists and possess KD values in the same range as those of the more flexible congener 3-diphenylacetoxy-quinuclidine (AF-43) and atropine (0.6--2 nM) but with koff = 0.1 msec-1 (AF-41) and koff = 1 msec-1 (AF-43) (carp atrium). Thus, duration of drug action of drug action at the receptor is a function of structural rigidity in the drug molecule, termination of action being fastest with the flexible molecules. Differences in rigidity among various antagonists also find expression in an unequal distribution of potencies in various tests; thus the rigid antagonists differentiate between two central effects in mice, viz., prevention of oxotremorine-induced tremors and fall from the rotating rod by a factor of 1:20 (especially AF-41 versus AF-43), whereas the more flexible antagonists (AF-43, atropine or even 3-quinuclidinyl-benzilate) do not show such as a selectivity. The existence of heterogenous muscarinic receptors can be inferred from data presented. Both theoretical and practical implications are discussed.
 ...
PMID:Does rigidity in structure of muscarinic agonists and antagonists reflect drug specificity? 723 38


1 2 3 Next >>