| Autor: |
Kachur JF, May EL, Awaya H, Egle JL Jr, Aceto MD, Martin BR |
| Jazyk: |
angličtina |
| Zdroj: |
Life sciences [Life Sci] 1986 Jan 27; Vol. 38 (4), pp. 323-30. |
| DOI: |
10.1016/0024-3205(86)90079-2 |
| Abstrakt: |
The racemate of a bridged-nicotine (BN) analog was synthesized and resolved into its enantiomers for pharmacological comparisons to (+)- and (-)-nicotine. The EC50 values for (-)- and (+)-nicotine and (-)- and (+)-BN were 4, 170, 53 and 400 microM, respectively, for producing contractions of guinea-pig ilea. (-)-Nicotine was an effective antinociceptive agent in the mouse tail-flick procedure at i.v. doses of 0.1-0.3 mg/kg, whereas the isomers of BN failed to alter tail-flick response in doses up to 5 mg/kg. (-)-Nicotine (0.01-0.3 mg/kg, i.v.) increased blood pressure and decreased heart rate in anesthetized rats. Neither (+)- nor (-)-BN altered blood pressure and heart rate in rats in this dosage range. At doses of 3-100 mg/kg, (+)-BN produced an increase in blood pressure without changing heart rate, while (-)-BN decreased both blood pressure and heart rate. Bridging the pyrrolidine and pyridine rings decreased biologic activity and did not result in stereoselectivity greater than that observed with (+)- and (-)-nicotine. It appears that there may be subpopulations of nicotine receptors to which the isomers of BN do not interact. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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