ISSN:
1432-1041
Keywords:
Key words Antipsychotic drug
;
Adverse drug reactions
;
Receptor affinity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Objective: This study was performed to determine whether in vitro affinities of currently available antipsychotics toward dopamine or other neuronal receptor systems are associated with their in vivo incidence of central and peripheral adverse drug reactions (ADRs). Methods: For 17 antipsychotic drugs available in Japan, the clinical incidences of 7 different types of drug-induced ADRs (i.e., akathisia, dyskinesia, tremor, rigidity, drowsiness, hypotension and dry mouth) were obtained from both post-marketing ADR databases and the investigational clinical trials of eight pharmaceutical companies. Affinity constants (K i) of the respective drugs toward dopamine D1 and D2 receptors, α1-adrenoceptors, histamine H1 receptors, serotonin 5-HT2 receptors and muscarinic cholinoceptors, determined using rat brain synaptosomes, were obtained from the literature. Relationships between in vitro receptor-binding properties and in vivo incidences of the respective types of antipsychotic-related ADRs were analyzed using Spearman's rank correlation. Results: Significant (P 〈 0.05) correlations were observed between the K i values for dopamine D2 receptor and the clinical incidences of akathisia and dyskinesia (r s = −0.68 and −0.66, respectively). Significant (P 〈 0.05) correlations were also observed between the K i values for α1-adrenoceptor and histamine H1 receptor and the incidence of drowsiness (r s=−0.65 and −0.55, respectively), and between the K i values for three receptor systems (i.e., dopamine D1 receptor, α1-adrenoceptor and histamine H1 receptor) and the incidence of dry mouth (r s = −0.50, −0.81 and −0.62, respectively). Conclusion: Preclinical receptor-binding data of antipsychotic drugs toward central dopamine and other ancillary neurotransmitter systems may be useful for predicting not only in vivo antipsychotic potency but also clinical incidence of akathisia and dyskinesia for this class of agents. Newly developed antipsychotic drugs with more potent and selective antagonistic activity against the dopamine D2 receptor may not necessarily be associated with a lower incidence of extrapyramidal ADRs.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050676
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