New 1-(heterocyclylalkyl)-4-(propionanilido)-4-piperidinyl methyl ester and methylene methyl ether analgesics.

A series of new 1-(heterocyclyalkyl)-4-(propionanilido)-4-piperidinyl methyl esters and methylene methyl ethers have been synthesized and pharmacologically evaluated. In the mouse hot-plate test, the majority of compounds exhibited an analgesia (ED50 less than 1 mg/kg) superior to that of morphine. These studies revealed a pharmacological accommodation for many more structurally diverse and far bulkier aromatic ring systems than the corresponding components of the arylethyl groups of the prototypic methyl ester (carfentanil, 2) and methylene methyl ether (sufentanil, 3 and alfentanil, 4) 4-propionanilido analgesics.

New 4-(heteroanilido)piperidines, structurally related to the pure opioid agonist fentanyl, with agonist and/or antagonist properties.

A research program based on certain heterocyclic modifications (12-50) of the fentanyl (1) molecule has generated a novel class of opioids. In the mouse hot-plate test, these compounds were weaker analgesics than 1. Two types of antagonists were observed in morphine-treated rabbits: those (e.

MAC of I-653 in beagle dogs and New Zealand white rabbits.

The minimum alveolar concentration (MAC) of I-653 was determined in six beagle dogs and four New Zealand white rabbits. The MAC values (+/- SD) were 7.2 +/- 1.

Development of acute tolerance to the cardiorespiratory effects of alfentanil after subsequent bolus injection in conscious rats.

The cardiovascular and respiratory effects of alfentanil in conscious freely moving rats, were evaluated after initial and subsequent injections. Doses of alfentanil (50, 130, 260, and 500 ug/kg) were given to naive rats (n = 4-5) and 1 hour later this dose was repeated. The resultant cardiovascular and respiratory effects were compared.