Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.
 ...
PMID:Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. 974 65

In view of a possible role of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) in neuroleptic-induced muscle rigidity and catalepsy, the present study is designed to investigate the neurochemical and extrapyramidal effects of atypical antipsychotic/neuroleptic drug i.e., Clozapine (CZP) on the metabolism of serotonin and dopamine particularly in the caudate (a region of the brain involved in the control of movement), accumbens and rest of the rat brain. Interaperitoneal (i.p) injections of CZP at doses of 5.0 & 10 mg/kg decreased significantly (p<0.01) locomotor activity in familiar (home cage) environment. CZP produced a significant (P<0.01) cataleptic response only at doses of 10 mg/kg used. Maximal cataleptic effects in rats occurred at high doses of CZP. Acute administration of CZP significantly (p<0.01) decreased levels of NA in accumbens at all the doses used. Significant increases (p<0.01) in the levels of NA observed in rest of the brain only at moderate dose (5 mg/kg) of CZP. Results showed significant (p<0.01) increases in the levels of caudate DA following the administration of CZP at 10 mg/kg. However administration of CZP at all the doses produced similar significant (p<0.01) increases in the levels of HVA in all the regions of the rat brain. Overall insignificant effects of CZP occurred on brain regional TRP. However, plasma TRP significantly (p<0.01) increased at 2.5 mg/kg dose of CZP. Administration of CZP at doses of 2.5 and 10 mg/kg significantly (p<0.01) decreased 5-HT levels in the rest of the brain. Administration of CZP produced insignificant (p>0.05) effects on 5-HIAA levels in the caudate and accumbens regions but CZP at doses of 2.5 and 5 mg/kg significantly (p<0.01) decreased 5-HIAA levels in the rest of the brain. Neurochemical and extrapyramidal effects of atypical antipsychotic (clozapine) are discussed in relation to a potential therapeutic profile in rats.
 ...
PMID:Neurochemical and extra pyramidal effects of atypical neuroleptic clozapine in rats. 1641 38