Pentazocine analgesic activity

Phenyl-2-azabicyclo[2.2.1]heptanes (27) have been synthesized via conventional routes by Takeda s group(21) as an extension of their arylmorphan and arylazabicyclo[3.2.1]octane studies. When R = H no analgesic activity was exhibited in the MW test however, curiously, the corresponding methyl ethers [e.g., 27 (R = Me)] were about x pentazocine as agonists. Some derivatives were moderate antagonists (— pentazocine). 

Pentasa mesalazine. pentazocine [ban,inn.jan,usan] (pentazocine hydrochloride [usan] pentazocine lactate [usan] NSC 107430 Fortagesic Fortral Talwin ) is one of the benzomorphan series and is a (mixed partial p and full k) OPIOID RECEPTOR AGONIST with OPIOID ANALGESIC activity. It is used orally or by injection to treat moderate to severe pain, pentazocine hydrochloride pentazocine, pentazocine lactate pentazocine, pentetrazol [ban, inn] (pentylenetetrazole pentamethylenetetrazole) has similar properties to doxapram as a CNS stimulant and respiratory stimulant. It was previously used intramuscularly to treat barbiturate and other CNS depressants in overdose, and orally for bronchial disorders. 

Studied a series of opiate antagonists based upon a 6,7-benzomorphan nucleus (3). One of these compounds, pentazocine (4), proved to be a useful analgesic agent since it was largely devoid of the psychotomimetic side-effects often elicited by other benzomorphans, yet it retained analgesic activity equivalent in potency to about half of that of morphine [17], with minimum addiction liability in man [18]. 

From the clinical standpoint the introduction of pentazocine as a non-addictive oral analgesic provided i he major landmark in the year under review. Scientifically, the demonstration (see below) that optical resolution of active analgesics can separate analgesic activity and narcotic antagonism will probably rank as the year s major advance. 

B. Benzomorphans - Clinical trials of the d 1 isomers of pentazocine (k) have shown "16 th both analgesic activity and side effects reside in the levo-isomer. Other trials, double-blind in many patients, confirm" 7,18 the activity of the compound at about one-third that of morphine, while measurements of respiratory depression in treated patients suggest" 9,20 this to be less than morphine at equianalgesic doses. The oral absorption has been determined2 1 and metabolic breakdown found22 to occur predominantly at the terminal methyl groups of the side chain. Reports of addiction to the injected form of pentazocine have been published ,24,25 including one to the oral form. 

As is well known by now, we synthesized a large number of benzomorphans and evaluated several in the clinic. Only two have been subjected to the rigorous examination for physical dependence capacity in Lexington. Neither cycla-zoclne nor pentazocine substitute for morphine in dependent subjects nor do they Induce a morphine-like primary dependence in post-addicts. There is no reason to believe that the other narcotic antagonists would behave differently. Some of the narcotic antagonists which have been studied over the past several years are shown in Chart II. The clinical analgesic activity is recorded in the last column of Table I. 

Nalbuphine hydrochloride is structurally related to oxymorphone and naloxone. It is approximately equipotent with morphine. Nalbuphine is metabolised in the liver to inactive metabolites. The plasma terminal half-life is approximately 5 h. The onset of analgesia is within 2-3 min of intravenous administration and 15 min after intramuscular injection, and lasts 3-6 h with an adult dose of 10 mg. With equi-analgesic doses, similar degrees of respiratory depression to that of morphine occur up to a dose of approximately 0.45 mg-kg-1. With higher doses a ceiling effect occurs. Sedation, possibly mediated by K-receptor activation, occasionally occurs. The incidence of psychotomimetic side effects is lower than with pentazocine. The abuse potential is low, but is can cause withdrawal symptoms in opioid-dependent subjects. It has occasionally been used to reverse opioid-induced respiratory depression. 

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