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Levorphanol but not dextrorphan suppresses the foot-lifting response to an aversive thermal stimulus in the terrestrial snail, Cepaea nemoralis.

The terrestrial snail, Cepaea nemoralis, when placed on a surface heated at 40 degrees C lifts the anterior portion of its foot from the source of heat. This stereotyped response, which suggests aversion, can be inhibited by injections of small doses of morphine and levorphanol, but is not affected by similar or larger doses of dextrorphan. It is suggested that the "analgesic" effect of the opiates in these animals involves interaction with stereochemically specific opiate receptors that may be fundamentally similar to those occurring in mammals.

Animals↗

Levorphanol-sensitive [3H]naloxone binding in developing brainstem following prenatal morphine exposure.

Levorphanol-sensitive [3H]naloxone binding was measured in brainstems of fetuses and postnatal offspring of rats injected with morphine or saline or pairfed with morphine-injected animals during the last half of gestation. Brainstem receptor concentrations in saline-injected animals decreased by 25% from gestation day 21 to postnatal day 60, while [3H]naloxone binding affinity doubled during the same interval. Chronic morphine exposure decreased receptor concentration at the 21st day of gestation by 28-48%, without changing binding affinity. However, the number and affinity of [3H]naloxone binding sites in morphine-injected animals were not different from controls at 60 days postnatally.

Animals↗

Synthesis and pharmacology of metabolically stable tert-butyl ethers of morphine and levorphanol.

3-O-tert-Butylmorphine (5) was prepared from 6-O-acetylmorphine (3) via alkylation with N,N-dimethylformamide di-tert-butyl acetal, followed by hydrolytic removal of the 3-(dimethylamino)-2-propenoate group. The same process was used to prepare the tert-butyl ether of levorphanol (6), (-)-3-tert-butoxy-N-methylmorphinan (8). Both 5 and 8 exhibited in vitro affinity for the opiate receptor comparable to codeine and had analgesic properties in the writhing test. Only 5 exhibited activity in the tail-flick procedure and neither compound showed significant antitussive activity.

Analgesics↗

[Studies on the analysis of anileridine, levorphanol, nalbuphine and ethamivan in urine].

The method for the analysis of anileridine, levorphanol, nalbuphine and ethamivan in urine by means of GC/NPD and GC/MSD is described. TFAA and MSTFA-MBTFA have been used in this procedure for TFA and TMS derivatization. The parent forms and the metabolites of the four drugs can be found by GC/NPD screening and GC/MSD confirmation. The method is reliable, fast and sensitive.

Benzamides↗

Changes in plasma corticosterone levels as a measure of acute dependence upon levorphanol in rats.

Changes in plasma corticosterone levels have been utilized as a sensitive and reliable indicator of opiate withdrawal. By using rats prepared with chronic indwelling i.v. catheters, drug injections and sequential blood sampling were accompanied in conscious undisturbed animals. Acute administration of levorphanol tartrate (LT) at 0.5, 1.0 or 2.0 mg/kg b.wt. caused an elevation in circulating corticosterone. With the lowest dose of LT, hormone levels returned to pretreatment values by 180 min. Naloxone hydrochloride (NX), 0.4 mg/kg, administered 3 hr after pretreatment with LT, 0.5 mg/kg, produced a significant elevation in plasma corticosterone. In contrast, animals pretreated with saline did not show the same increase in hormone levels after NX. NX, administered at several doses, along with LT, suppressed the plasma corticosterone increase which is normally observed when LT is given acutely. When NX is administered at sufficient dosage, along with LT pretreatment, the subsequent administration of the antagonist did not elicit the withdrawal response. These data indicate that a similar increase in plasma corticosterone, upon challenge with NX after a single dose of morphine, generalizes to other opiates. Blockade of the initial rise in plasma corticosterone and subsequent increase upon injection of the antagonist speak to the probability of the responses being related and opiate specific.

Animals↗