Codeine blood-brain-barrier

Opiates are drugs that exert their beneficial actions through the CNS, and although codeine and heroin have a reasonable level of passage across the blood-brain barrier, morphine s passage is much lower/419 ... 

Morphine is a strong agonist that crosses easily into the CNS. It is highly potent with regard to CNS effects, such as euphoria and medullary respiratory depression. Codeine is also a strong to moderate agonist, but does not cross the blood-brain barrier well. Thus, higher doses are needed to achieve CNS effects. Loperamide has little ability to cross into the CNS and is unlikely to produce CNS effects at any dose. It is thus sold over-the-counter. 

When morphine and most opioids are given intravenously, they act promptly. However, the more lipid-soluble compounds act more rapidly than morphine after subcutaneous administration because of differences in the rates of absorption and entry into the CNS. Compared with more lipid-soluble opioids such as codeine, heroin, and methadone, morphine crosses the blood-brain barrier... 

Xie R, Hammarlund-Udenaes M (1998) Blood-brain barrier equilibration of codeine in rats studied with microdialysis. Pharm Res 15 570-575... 

Morphine has an LD50 i.v. in mouse of 226-318 mg/kg (Wink, 1993). Codeine (62) is also an important analgetic and antitussive drug. Codeine is the most widely used morphine type alkaloid it has an LD50 i.p. in mouse of 300 mg/kg (Wink, 1993). This alkaloid is derived from opium (0.2-0.7%) and synthesized by methylation of morphine (Tyler et al, 1981). Heroin (65) (Fig. 32.21), a synthetic diacetate of morphine, crosses the blood-brain barrier more rapidly than morphine and is highly euphoric and analgetic. 

---