PHAR 435 Lecture Notes - Lecture 3: Thiophene, Switch, Signal Transduction

• School: UBC
• Department: Pharmaceutical Sciences
• Course: PHAR 435
• Professor: Stelvio Bandiera

Document Summary

Effects of opioids = pe(cid:396)(cid:272)eptio(cid:374) of pai(cid:374), (cid:396)ea(cid:272)tio(cid:374) to pai(cid:374), pai(cid:374) tolerance. Moa at the -opioid receptor: the -or couples predominantly to the g protein gi (gi/o, opioid agonists reduce neuro(cid:374)al e(cid:454)(cid:272)ita(cid:271)ilit(cid:455) (cid:271)(cid:455) ca e(cid:374)t(cid:396)(cid:455), Out(cid:449)a(cid:396)d (cid:373)o(cid:448)e(cid:373)e(cid:374)t of k+ (cid:448)ia girk"s, ade(cid:374)(cid:455)late (cid:272)(cid:455)(cid:272)lase. Phenolic oh group at c-(cid:1007) that"s acidic (pka 9. 9) Basic nitrogen (n-17) pka 8. 0 protonated at ph. C-14 h replaced by an oh in certain opioids. In vitro, the quaternary salt has activity, but in vivo it loses its affinity the (cid:395)uate(cid:396)(cid:374)a(cid:396)(cid:455) salt does(cid:374)"t (cid:272)(cid:396)oss the bbb. Larger alkyl groups: binding in tact, but loss of activity: as you increase size, you decrease the ability to break key toggle switches. But when you add a phenyl group, the affinity actually increases and is a more potent agonist than morphine not understood why this occurs. Most important modification is the formation of hydromorphone: The 2 modifications increase its lipophilicity = able to cross the bbb.