Blockade of central beta-adrenoceptors attenuates tremor induced by 5-hydroxytryptamine (5-HT)-receptor activation in rats.
The effect of beta-adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited by L-5-hydroxytryptophan (L-5-HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Plasma levels of the beta-adrenoceptor antagonists were determined simultaneously. The non-selective lipophilic adrenoceptor antagonist propranolol was found to dose-dependently reduce tremor intensity, whereas the non-selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, beta 1-selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the beta 2-selective antagonist ICI 118,551 dose-dependently suppressed tremor intensity, suggesting that the beta-adrenoceptor subtype involved is of the beta 2-type. These results suggest that blockade of centrally located beta 2-adrenoceptors are able to attenuate the tremor response following 5-hydroxytryptamine receptor activation.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy*
D000319:Adrenergic beta-Antagonists; D008732:Methoxydimethyltryptamines; D011412:Propanolamines; D011985:Receptors, Serotonin; C026777:ICI 118551; D011433:Propranolol; D013015:Sotalol; D006916:5-Hydroxytryptophan; D008790:Metoprolol