Raymond P. Ahlquist

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Raymond Perry Ahlquist (born July 26, 1914 in Missoula , Montana , † April 15, 1983 in Augusta , Georgia ) was an American pharmacist and pharmacologist . With his subdivision of the adrenoceptors into α- and β-adrenoceptors, published in 1948, he contributed significantly to the explanation of the effects of known and the development of new drugs .

Life

Both parents were from Sweden. His father was an auditor for the Northern Pacific Railway . In 1940, the son earned a Ph.D. from the University of Washington in Seattle. -Doctoral Degree in Pharmacology. In Seattle he also met his wife Dorotha Duff Ahlquist. There followed four years at South Dakota State University in Brookings . Then he entered the Medical College of Georgia in Augusta. There he held the chair of pharmacology from 1948 to 1963, was Associate Dean for Basic Sciences from 1963 to 1970 , i.e. responsible for basic research in the dean's office , then returned to the chair until 1977 and finally held an honorary professorship until his death .

plant

The adrenoceptor breakdown

In South Dakota, a replacement was sought for the ephedrine, which comes from a Chinese plant and is therefore scarce . Similar to adrenaline and noradrenaline , it is a sympathomimetic , i.e. a substance that mimics the effects of the sympathetic nervous system . This is how Ahlquist came up with his subject. The mode of action of sympathomimetics confused pharmacologists and physiologists at the time . There were inhibitory and excitatory effects, some that could be blocked by antagonists such as ergot alkaloids , and others that could not.

For his famous work, Ahlquist, now in Georgia, selected six sympathomimetics, including adrenaline, noradrenaline, α-methylnoradrenaline and isoprenaline , and examined their effects on several organs, including the blood vessels and the heart. He found that the six substances had two and only two orders of effectiveness on the various organs. For example, in the order “adrenaline> noradrenaline> α-methylnoradrenaline> isoprenaline” they contracted blood vessels, but in the order “isoprenaline> adrenaline> α-methylnoradrenaline> noradrenaline” they stimulated the heart. Ahlquist concluded that there are two different receptors for sympathomimetics. The receptors with the first-mentioned order of effectiveness (e.g. for blood vessel contraction, but also for dilation of the pupil), he called α-adrenoceptors ( alpha adrenotropic receptor), the receptors with the second order of effectiveness (for example, for promoting heart activity, but also for Expansion of the bronchi ), he called β-adrenoceptors.

Just as restrictive as it was forward-looking, he wrote (from English): “At the moment, little can be said about the nature of adrenoceptors and the difference between the α and β types; however, the subdivision concept should be useful in researching the various effects of adrenaline and other sympathomimetics and the effects of the sympathetic nervous system. "

The publication experienced early misunderstanding and late success. The manuscript was rejected by the “responsible” Journal of Pharmacology and Experimental Therapeutics and then accepted for publication by the American Journal of Physiology . As for Ahlquist's question about the nature of adrenoceptors, we now know that they are glycoproteins and that humans have nine adrenoceptor genes and thus nine different adrenoceptors, α 1A , α 1B , α 1D , α 2A , α 2B , α 2C , β 1 , β 2 and β 3 . Ahlquist laid the foundation for this. In drug therapy, for example, he laid the foundation for the development of beta blockers for the treatment of heart disease and high blood pressure .

More work

Ahlquist's other scientific work is also mainly concerned with the pharmacology of the sympathetic nervous system. So he did research on tolazoline , a substance with a completely different chemical structure than adrenaline and noradrenaline. When dichloroisoprenaline, the first clinically useless beta blocker, was discovered in 1958, he recognized with its help that the intestinal peristalsis is inhibited by both α and β adrenoceptors.

In what was probably his last essay in 1980, he looked back at the 1948 publication. Their exceptional character is also evident from a bibliometric citation analysis . It is Ahlquist's most frequently cited work; to date (2011) it has been cited 2766 times, the second most frequently cited - via the intestinal adrenoceptors - only 266 times.

recognition

Ahlquist was honored with the Oscar B. Hunter Memorial Award in Therapeutics , the Ciba Prize for Hypertension Research , and the Albert Lasker Award for Clinical Medical Research .

Web links

Individual evidence

  1. ↑ JHR Sutherland, GO Carrier and LM Greenbaum: Dr. Raymond P. Ahlquist . In: The Pharmacologist . 25, No. 1, 1983, p. 73.
  2. ^ RC Little: Raymond P. Ahlquist (1914-1983) . In: Clinical Cardiology . 10, 1987, pp. 583-584. doi : 10.1002 / clc.4960110815 .
  3. ^ A b Raymond P. Ahlquist: A study of the adrenotropic receptors . In: American Journal of Physiology . 153, 1948, pp. 586-600.
  4. ↑ Klaus Starke: The history of the α-adrenoceptor agonists. In: Pharmacy in our time , in press
  5. ↑ Raymond P. Ahlquist, Russell A. Huggins and RA Woodbury: The pharmacology of benzyl-imidazoline (Priscol). . In: Journal of Pharmacology and Experimental Therapeutics . 89, 1947, pp. 271-288.
  6. ^ Raymond P. Ahlquist and Bernard Levy: Adrenergic receptive mechanism of canine ileum. . In: Journal of Pharmacology and Experimental Therapeutics . 127, 1959, pp. 146-149.
  7. ^ RP Ahlquist: Historical perspective: classification of adrenoreceptors . In: Journal of Autonomic Pharmacology . 1, 1980, pp. 101-106. doi : 10.1111 / j.1474-8673.1980.tb00445.x .
personal data
SURNAME Ahlquist, Raymond P.
ALTERNATIVE NAMES Ahlquist, Raymond Perry (full name)
BRIEF DESCRIPTION American pharmacist and pharmacologist
DATE OF BIRTH July 26, 1914
PLACE OF BIRTH Missoula , Montana
DATE OF DEATH April 15, 1983
Place of death Augusta , Georgia